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TABLE OF CONTENTS
LIST OF IN-TEXT TABLES ....................................................................................................5
LIST OF IN-TEXT FIGURES...................................................................................................8
ABBREVIATIONS .................................................................................................................10
2.7.4. SUMMARY OF CLINICAL SAFETY .........................................................................13
2.7.4.1. Exposure to BNT162b2.....................................................................................172.7.4.1.1. Overall Safety Evaluation Plan and Narratives of Safety Studies ........172.7.4.1.1.1. Phase 1/2 Study BNT162-01...............................................18
2.7.4.1.1.2. Pivotal Phase 1/2/3 Safety, Immunogenicity, andEfficacy Study C4591001..................................................................21
2.7.4.1.1.3. Narratives ............................................................................33
2.7.4.1.2. Overall Extent of Exposure, Disposition, and Study Population
Characteristics..................................................................................................34

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2.7.4.1.2.1. Study BNT162-01 ...............................................................34
2.7.4.1.2.2. Phase 1 (Study C4591001) ..................................................35
2.7.4.1.2.3. Phase 2 (Study C4591001) ..................................................37
2.7.4.1.2.4. Phase 3 (Study C4591001) ..................................................38
2.7.4.2. Safety Results for BNT162b2 ...........................................................................46
2.7.4.2.1. Study BNT162-01.................................................................................47
2.7.4.2.1.1. Reactogenicity (Phase 1, Study BNT162-01) .....................47
2.7.4.2.1.2. Summary of Treatment-Emergent Adverse Events(Phase 1, Study BNT162-01) ............................................................48
2.7.4.2.1.3. Analysis of Treatment-Emergent Adverse Events(Phase 1, Study BNT162-01) ............................................................48
2.7.4.2.1.4. Deaths, Serious Adverse Events, Safety-Related
Participant Withdrawals, and Other Significant Adverse Events(Phase 1, Study BNT162-01) ............................................................49
2.7.4.2.1.5. Clinical Laboratory Evaluations (Phase 1, Study
BNT162-01) ......................................................................................50
2.7.4.2.1.6. Vital Signs, Physical Findings, and Other
Observations Related to Safety (Phase 1, Study BNT162-01)..........50
2.7.4.2.1.7. Conclusions (Phase 1, Study BNT162-01) .........................51
2.7.4.2.2. Phase 1 (Study C4591001) ...................................................................51
2.7.4.2.2.1. Reactogenicity (Phase 1, Study C4591001)........................51

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2.7.4.2.2.2. Summary of Adverse Events (Phase 1, Study
C4591001) .........................................................................................52
2.7.4.2.2.3. Analysis of Adverse Events (Phase 1, Study
C4591001) .........................................................................................53
2.7.4.2.2.4. Deaths, Serious Adverse Events, Safety-Related
Participant Withdrawals, and Other Significant Adverse Events(Phase 1, Study C4591001) ...............................................................54
2.7.4.2.2.5. Clinical Laboratory Evaluations (Phase 1, Study
C4591001) .........................................................................................55
2.7.4.2.2.6. Physical Examination Findings (Phase 1, Study
C4591001) .........................................................................................55
2.7.4.2.2.7. Narratives (Phase 1, Study C4591001) ...............................55
2.7.4.2.2.8. Conclusions (Phase 1, Study C4591001) ............................56
2.7.4.2.3. Phase 2 (Study C4591001) ...................................................................56

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2.7.4.2.3.1. Reactogenicity (Phase 2, Study C4591001)........................56
2.7.4.2.3.2. Summary of Adverse Events (Phase 2, Study
C4591001) .........................................................................................58
2.7.4.2.3.3. Analysis of Adverse Events (Phase 2, Study
C4591001) .........................................................................................59
2.7.4.2.3.4. Deaths, Serious Adverse Events, Safety-Related
Participant Withdrawals, and Other Significant Adverse Events(Phase 2, Study C4591001) ...............................................................60
2.7.4.2.3.5. Narratives (Phase 2, Study C4591001) ...............................60
2.7.4.2.3.6. Conclusions (Phase 2, Study C4591001) ............................60
2.7.4.2.4. Phase 3 (Study C4591001) ...................................................................61
2.7.4.2.4.1. Reactogenicity (Phase 3, Study C4591001)........................61
2.7.4.2.4.2. Adverse Events (Phase 3, Study C4591001).......................73
2.7.4.2.4.3. Deaths, Serious Adverse Events, Safety-Related
Participant Withdrawals, and Other Significant Adverse Events(Phase 3, Study C4591001) .............................................................218
2.7.4.2.4.4. Narratives (Phase 3, Study C4591001) .............................290
2.7.4.2.4.5. Conclusions (Phase 3, Study C4591001) ..........................291
2.7.4.2.5. Discussion...........................................................................................291
2.7.4.3. Safety in Special Groups and Situations .........................................................294
2.7.4.3.1. Intrinsic Factors ..................................................................................294
2.7.4.3.1.1. Geriatric Use .....................................................................294
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2.7.4.3.1.2. Pediatric Use .....................................................................294
2.7.4.3.1.3. Use in Immunocompromised Individuals .........................294
2.7.4.3.2. Extrinsic Factors .................................................................................295
2.7.4.3.3. Drug Interactions ................................................................................295
2.7.4.3.4. Use in Pregnancy and Lactation .........................................................295
2.7.4.3.5. Overdose .............................................................................................295
2.7.4.3.6. Drug Abuse.........................................................................................295
2.7.4.3.7. Withdrawal and Rebound ...................................................................296
2.7.4.3.8. Effects on Ability to Drive or Operate Machinery or Impairmentof Mental Ability............................................................................................296
2.7.4.4. Post-Authorization Data ..................................................................................296
2.7.4.5. Overall Conclusions ........................................................................................296
2.7.4.6. APPENDICES.................................................................................................298

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2.7.4.6.1. Appendix A: Study BNT162-01 Safety Evaluation Plan ...................298
2.7.4.6.1.1. Study BNT162-01 Part A Study Schema ..........................298
2.7.4.6.1.2. Schedule of Activities (Study BNT162-01) ......................299
2.7.4.6.1.3. Study BNT162-01: Safety Assessments ...........................302
2.7.4.6.2. Appendix B: Study C4591001 Safety Evaluation Plan ......................305
2.7.4.6.2.1. Study C4591001 Study Schema ........................................305
2.7.4.6.2.2. Schedule of Activities (Study C4591001).........................306
2.7.4.6.2.3. Study C4591001: Safety Assessments ..............................320
2.7.4.6.3. Appendix C: Phase 2 Study C4591001 Post-text Tables....................327
2.7.4.6.3.1. Reactogenicity (Phase 2, Study C4591001, Post-text
Tables and Figures) .........................................................................327
2.7.4.6.4. Appendix D: Phase 3 Study C4591001 Post-text Tables ...................333
2.7.4.6.4.1. Exposure, Disposition, and Study Population
Characteristics (Phase 3, Study C4591001, Post-text Tables) ........333
2.7.4.7. REFERENCES................................................................................................344

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LIST OF IN-TEXT TABLES
Table 1.

Cutoff Dates for Safety Data Presented in Summary of Clinical
Safety ........................................................................................................16

Table 2.

Safety Objectives and Endpoints for Study BNT162-01..........................18

Table 3.

Safety Objectives, Estimands, and Endpoints for Study C4591001.........22

Table 4.

Demographic Characteristics – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population ...........................................................................43

Table 5.

Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 1 Month After Dose 2 – Blinded Placebo-Controlled
Follow-up Period – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population .................................................................................................76

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class andPreferred Term – Blinded Placebo-Controlled Follow-up Period –Phase 2/3 Subjects ≥16 Years of Age – Safety Population ......................82

Table 7.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to
Unblinding Date – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ...............................................................................................116

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population ....................120

Table 9.

Incidence Rates of at Least 1 Adverse Event From Unblinding Date
to Data Cutoff Date (13MAR2021) – Open-Label Follow-up Period– Subjects Who Originally Received BNT162b2 – Phase 2/3
Subjects ≥16 Years of Age – Safety Population.....................................160

Table 10.

Incidence Rates of at Least 1 Adverse Event From Unblinding Date
to Data Cutoff Date (13MAR2021), by System Organ Class andPreferred Term – Open-Label Follow-up Period – Subjects Who
Originally Received BNT162b2 – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population .........................................................................162

Table 11.

Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2 – Subjects With at Least 6
Months of Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16
Years of Age (Subjects Who Originally Received BNT162b2) –Safety Population....................................................................................170

Table 12.

Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2, by Time Period – Subjects Withat Least 6 Months of Follow-up Time After Dose 2 – Phase 2/3
Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population ............................................................171

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Table 13.

Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class andPreferred Term – Subjects With at Least 6 Months of Follow-up
Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age(Subjects Who Originally Received BNT162b2) – Safety
Population ...............................................................................................173

Table 14.

Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021) – Open-Label Follow-up Period –Subjects Who Originally Received Placebo and Then Received
BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population .........................................................................197

Table 15.

Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived Placebo and Then Received BNT162b2 After Unblinding– Phase 2/3 Subjects ≥16 Years of Age – Safety Population .................201

Table 16.

Incidence Rates of Deaths From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects≥16 Years of Age – Safety Population ...................................................219

Table 17.

Number (%) of Subjects Reporting at Least 1 Serious Adverse
Event From Dose 1 to 1 Month After Dose 2, by System OrganClass and Preferred Term – Blinded Placebo-Controlled Follow-up
Period – Phase 2/3 Subjects ≥16 Years of Age – Safety Population......222

Table 18.

Incidence Rates of at Least 1 Serious Adverse Event From Dose 1
to Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population ....................229

Table 19.

Incidence Rates of at Least 1 Serious Adverse Event From
Unblinding Date to Data Cutoff Date (13MAR2021), by System
Organ Class and Preferred Term – Open-Label Follow-up Period –Subjects Who Originally Received BNT162b2 – Phase 2/3 Subjects≥16 Years of Age – Safety Population ...................................................242

Table 20.

Number (%) of Subjects Reporting at Least 1 Serious Adverse
Event From Dose 1 to 6 Months After Dose 2, by System OrganClass and Preferred Term – Subjects With at Least 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years ofAge (Subjects Who Originally Received BNT162b2) – Safety
Population ...............................................................................................246

Table 21.

Incidence Rates of at Least 1 Serious Adverse Event From Dose 3
to Data Cutoff Date (13MAR2021), by System Organ Class andPreferred Term – Open-Label Follow-up Period – Subjects Who
Originally Received Placebo and Then Received BNT162b2 After
Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ...............................................................................................253
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Table 22.

Number (%) of Subjects Withdrawn Because of Adverse Events
From Dose 1 to 1 Month After Dose 2, by System Organ Class andPreferred Term – Blinded Placebo-Controlled Follow-up Period –Phase 2/3 Subjects ≥16 Years of Age – Safety Population ....................259

Table 23.

Incidence Rates of Subjects Withdrawn Because of Adverse Events
From Dose 1 to Unblinding Date, by System Organ Class andPreferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ...............................................................................................263

Table 24.

Incidence Rates of Subjects Withdrawn Because of Adverse Events
From Unblinding Date to Data Cutoff Date (13MAR2021), by
System Organ Class and Preferred Term – Open-Label Follow-up
Period – Subjects Who Originally Received BNT162b2 – Phase 2/3
Subjects ≥16 Years of Age – Safety Population.....................................267

Table 25.

Number (%) of Subjects Withdrawn Because of Adverse Events
From Dose 1 to 6 Months After Dose 2, by System Organ Class andPreferred Term – Subjects With at Least 6 Months of Follow-up
Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age(Subjects Who Originally Received BNT162b2) – Safety
Population ...............................................................................................268

Table 26.

Incidence Rates of Subjects Withdrawn Because of Adverse Events
From Dose 3 to Data Cutoff Date (13MAR2021), by System OrganClass and Preferred Term – Open-Label Follow-up Period –Subjects Who Originally Received Placebo and Then Received
BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population .........................................................................269

Table 27.

Selected Standard MedDRA Queries From Dose 1 to Unblinding
Date – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population.....................................274

Table 28.

Incidence Rates of at Least 1 Adverse Event Category of Special
Interest From Dose 1 to Unblinding Date, by Adverse Event
Category and Preferred Term – Blinded Placebo-Controlled
Follow-up Period – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ...............................................................................................281

Table 29.

Local Reaction Grading Scale (Study C4591001)..................................321

Table 30.

Systemic Event Grading Scale (Study C4591001).................................322

Table 31.

Disposition of All Randomized Subjects – Phase 2/3 Subjects ≥16
Years of Age ...........................................................................................333

Table 32.

Vaccine as Administered by Vaccine Group – Phase 2/3 Subjects≥16 Years of Age – All Randomized Subjects.......................................336

Table 33.

Vaccine Administration Timing – Phase 2/3 Subjects ≥16 Years of
Age – All Randomized Subjects.............................................................337
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Table 34.

Safety Population – Phase 2/3 Subjects ≥16 Years of Age ....................338

Table 35.

Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population .........................................................................339

Table 36.

Demographic Characteristics – Subjects With at Least 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years ofAge (Subjects Who Originally Received BNT162b2) – Safety
Population ...............................................................................................340

Table 37.

Demographic Characteristics – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After Unblinding – Phase
2/3 Subjects ≥16 Years of Age – Safety Population...............................342

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LIST OF IN-TEXT FIGURES
Figure 1.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose, by Age Group (Reactogenicity Subset) –Phase 2/3 Subjects ≥16 Years of Age – Safety Population AgeGroup: 16 Through 55 Years of Age – Safety Population .......................63

Figure 2.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose, by Age Group (Reactogenicity Subset) –Phase 2/3 Subjects ≥16 Years of Age – Safety Population AgeGroup: >55 Years of Age .........................................................................64

Figure 3.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose (Reactogenicity Subset) – Blinded
Placebo-Controlled Follow-up Period – Phase 2/3 HIV-Positive
Subjects ≥16 Years of Age – Safety Population.......................................66

Figure 4.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose, by Age Group (Reactogenicity
Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: 16 Through 55 Years ............................................................69

Figure 5.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose, Age Group (Reactogenicity
Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: >55 Years..............................................................................70

Figure 6.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose (Reactogenicity Subset) – Blinded
Placebo-Controlled Follow-up Period – Phase 2/3 HIV-Positive
Subjects ≥16 Years of Age – Safety Population.......................................72

Figure 7

Study C4591001 Phase 3 Safety Analyses: Time Periods andAnalysis Groups........................................................................................74

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Figure 8.

Forest Plot of Tier 2 Adverse Events Reported From Dose 1 to 1
Month After Dose 2 – Blinded Placebo-Controlled Follow-up
Period – Phase 2/3 Subjects ≥16 Years of Age – Safety Population........78

Figure 9.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose – Phase 2 – Safety Population.........................327

Figure 10.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose, Phase 2 - Age Group: 18-55 Years –Safety Population....................................................................................328

Figure 11.

Subjects Reporting Local Reactions, by Maximum Severity, Within
7 Days After Each Dose, Phase 2 – Age Group: 56-85 Years –Safety Population....................................................................................329

Figure 12.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose – Phase 2 – Safety Population ............330

Figure 13.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose, Phase 2 – Age Group: 18-55 Years– Safety Population.................................................................................331

Figure 14.

Subjects Reporting Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose, Phase 2 – Age Group: 56-85 Years– Phase 2 – Safety Population ................................................................332

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090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)ABBREVIATIONS
Abbreviation

Definition

ADR

adverse drug reactionAE

adverse event

AESI

adverse events of special interest

ALT

alanine aminotransferase

AST

aspartate aminotransferase

BLA

Biologics License Application

BMI

body mass index

BUN

blood urea nitrogen

C4591001 Efficacy
Final Analysis
Interim CSR

Study C4591001 interim clinical study report including prespecified final analysis ofefficacy and available immunogenicity and safety data up to data cutoff date of 14
November 2020

C4591001 6-Month
Update Interim CSR

Study C4591001 interim clinical study report including updated efficacy,
immunogenicity, and safety up to 6 months after Dose 2 up to data cutoff date of 13
March 2021

CBER

(US Food and Drug Administration) Center for Biologics Evaluation and Research

CDC(US) Centers for Disease Control and Prevention

CDS

Core Data SheetCI

confidence interval

CO

Clinical Overview

COVID-19

Coronavirus Disease 2019

CRF

case report form

CRP

c-reactive protein

CSR

Clinical Study Report

CTA

Clinical Trial Application

DART

Developmental and Reproductive Toxicology

DMC(US Study C4591001) Data Monitoring Committee

ECG

electrocardiogram

EoS

end of study

FDA(US) Food and Drug Administration

FIH

first-in-humanFUfollow-up

HBV

hepatitis B virus
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Abbreviation

Definition

HBc Abs

hepatitis B core antibodies

HBsAg

hepatitis B surface antigen

HCV

hepatitis C virus

HCV Abs

hepatitis C virus antibodiesHIVhuman immunodeficiency virus

HLThigh level term

ICD

informed consent document

IgG

immunoglobulin G

IgM

immunoglobulin M

IMintramuscular(ly)IND

Investigational New DrugIR

incidence rate

IRC

(US Study C4591001) Internal Review Committee

IRTinteractive response technology

IVintravenous

IWR

interactive Web-based response

LLN

lower limit of normal

MedDRA

Medical Dictionary for Regulatory Activities

MIS-C

multisystem inflammatory syndrome in children

NAAT

nucleic acid amplification testing

NHP

non-human primate

P/B

prime/boost: dosing regimen of a priming immunization and a booster immunization

PCR

polymerase chain reaction

PT

Preferred Term

PY

person-years

RNAribonucleic acidSAF

Safety Set

SAP

statistical analysis plan

SAE

serious adverse event

SARS-CoV-2

SARS Coronavirus-2; virus causing the disease COVID-19

SCE

Summary of Clinical Efficacy

SCS

Summary of Clinical Safety
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Abbreviation

Definition

SIRVA

shoulder injury related to vaccine administration

SMQ

Standardised MedDRA Queries

SoAschedule of activities

SOC

System Organ Class

SRC

Safety Review Committee

US

United States

VOC

variant of concern

TEAE

treatment-emergent adverse events

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2.7.4. SUMMARY OF CLINICAL SAFETY
This SCS presents the safety and tolerability data for BNT162b2. BNT162b2 (BioNTech
code number BNT162, Pfizer code number PF-07302048) is an investigational vaccine
developed by BioNTech and Pfizer intended to prevent COVID-19, which is caused by
SARS-CoV-2. The data are derived from the pivotal registration study, Phase 1/2/3 Study
C4591001 (BNT162-02), conducted under IND 19736. Supporting data are presented fromthe FIH, dose level-finding, Phase 1/2 Study BNT162-01 conducted in Germany (which is
not being conducted under the IND, but under a CTA).
The proposed indication and dosing administration for BNT162b2 (30 µg) is:Proposed indication: Active immunization against COVID-19 disease caused by
SARS-CoV-2 virus in individuals ≥16 years of age.

Proposed dosing administration: single 0.3 mL intramuscular (IM) dose followed by asecond 0.3 mL dose 21 days later.

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Nonclinical studies in this development program are summarized in the CO (Module 2.5
Section 2.5.1.2.3.1).
Phase 1 of Study C4591001 evaluated 2 vaccine candidates, BNT162b1 and BNT162b2.
These 2 candidates were selected based on safety and immunogenicity data from
Study BNT162-01 (which is evaluating four vaccine candidates). Phase 1 of Study C4591001
comprised of dose-level finding evaluations of the 2 selected vaccine candidates; multiple
dose levels were evaluated, including some that corresponded to those evaluated inStudy BNT162-01 (BNT162b1 and BNT162b2 at 10 µg, 20 µg, and 30 µg). Study vaccine
was administered using the same 2-dose regimen as in Study BNT162-01 (21 days apart).
Dose levels were administered first to an 18 to 55 years of age cohort, then to a 65 to
85 years of age cohort.
Evaluation of Phase 1 safety and immunogenicity results led to the selection of a single
candidate. Both constructs were safe and well tolerated (except for BNT162b1 at 100 μg).
Given that the reactogenicity profile for BNT162b2 was more favorable than BNT162b1 in
both younger and older adults with similar immunogenicity results, and with non-humanprimate (NHP) challenge studies showing that BNT162b2 led to earlier virus clearance andno evidence of virus in the lung, BNT162b2 at the 30 µg dose level was selected andadvanced into the Phase 2/3 expanded cohort and efficacy evaluation.
Phase 2 of the study (for which enrollment has completed) comprised the evaluation of safety
and immunogenicity data for the first 360 participants (180 from active vaccine group and
180 from placebo group) that entered the study after completion of Phase 1.
The Phase 3 part of the study is ongoing, and participants (including the first 360 participantsfrom Phase 2) are continuing to be evaluated at the time of this SCS. The minimum age forinclusion in Phase 3 was lowered from 18 to 16 years of age after the approval of
Study C4591001 protocol amendment 6 and from 16 to 12 years of age after the approval of

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Study C4591001 protocol amendment 7. As such, Phase 3 has completed enrollment ofadolescents ≥12 years of age (stratified as 12-15, 16-55, or >55 years of age).

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C4591001 protocol amendment 10 allowed participants ≥16 years of age who originallyreceived placebo the opportunity to receive BNT162b2 following local or national
recommendations, or following completion of the active safety surveillance period. On
14 December 2020, the process of disclosing vaccine assignments for all trial participants≥16 years of age began. Hence, for each trial participant, there are 2 periods in the study:
enrollment into the observer-blind phase until the date of vaccine disclosure and the time inthe study after disclosure. Participants who originally were randomized to BNT162b2, arecontinuing to be followed for safety as specified in the protocol. The safety data forparticipants who originally were randomized to and received placebo prior to disclosure of
vaccine assignment are standard blinded data that contribute to controlled assessment ofsafety compared to individuals who randomly assigned to BNT162b2. After vaccine
treatment disclosure and the administration of BNT162b2, the placebo participants can nolonger be used for direct comparison with those who originally were randomized to
BNT162b2. Given that individuals were unblinded on different days after
14 December 2020, the analysis of the observer-blinded, placebo-controlled portion of thestudy as well as the open-label portion displays rates of AEs adjusted for exposure time.
Safety data for Phase 3 of Study C4591001, based on the data cutoff date of 13 March 2021,
presented in this SCS include:Blinded placebo-controlled period: Dose 1 to 1 month after Dose 2 and to unblindingdate:o Phase 1 participants randomized to BNT162b2 30 µg (up to ~6 months after
Dose 2)o Phase 2/3 ≥16 years of age participants including HIV+ subset (up to ~6months after Dose 2)

Open-label observational period: from time of unblinding to data cutoff date:o Phase 2/3 participants ≥16 years of age originally randomized to BNT162b2
o Phase 2/3 participants ≥16 years of age originally randomized to placebo whothen received BNT162b2



Cumulative follow-up from Dose 1 to 6 months after Dose 2: Phase 2/3 participantsoriginally randomized to BNT162b2 (inclusive of blinded data and open-label data)comprised of at least 3000 in each age group (16 to 55 years of age, >55 years of age)

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Overall, this SCS summarizes the safety data obtained from Study C4591001 (Phases 1 to 3)
and Study BNT162-01 (Phase 1) to support registration of BNT162b2. The following data
are presented in this document by study and phase:The overall safety evaluation plans for each study (including objectives, endpoints,
methods, and criteria for narratives) are presented in Section 2.7.4.1.1.

Data regarding exposure, disposition, and study population characteristics arepresented in Section 2.7.4.1.2.

The results of safety evaluations are presented in Section 2.7.4.2. These evaluations
include:o Reactogenicity (local reactions and systemic events)o AEs (by SOC, related, immediate, severe, deaths, SAEs, and withdrawals due
to AEs)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)o Other safety assessmentso Narratives
Safety in special groups and situations is presented in Section 2.7.4.3.



Post-Authorization Data in Section 2.7.4.4.

Overall conclusions are stated in Section 2.7.4.5.

The safety results presented in this SCS demonstrate that BNT162b2 is both safe andwell-tolerated when administered on a 2-dose schedule (21 days apart) in individuals≥16 years of age. The cutoff dates for safety data presented in this SCS are shown in Table 1.

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Table 1.

Cutoff Dates for Safety Data Presented in Summary of Clinical Safety

Phase/Study

Safety Data Available (Through)Study
BNT162-01

Reactogenicity: up to 7 days after
each dose
AEs: 1 month post-dose 2
Reactogenicity: up to 7 days after
each dose

Phase 1
(StudyC4591001)

N (number
randomized)
216

Age(years of age)
Younger: 18 to 55
Older: 56 to 85

Data Cutoff
Date
23 Oct 2020

195

Younger: 18 to 55
Older: 65 to 85

24 Aug2020

AEs: 1 month post-dose 2
SAEs: through the data cutoff date
Laboratory Data: 7 days post-dose 2090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

BNT162b1 100 µg dose level(younger age group): 3 weeks postdose 1 or to before Dose 2 (based on
the data cutoff date)Long-term follow-up for AEs & SAEs
for BNT162b2 30 µg group only: From 1 month post-dose 2 to
unblinding date(approximately 6 months
post-dose 2)

Phase 2
(StudyC4591001)

Reactogenicity: up to 7 days after
each dose

13 Mar 2021
30

360b

AEs/SAEs: 7 days post-dose 2a

18 to 85
 Younger: 18
to 55
 Older: 56 to85

02 Sep 2020

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 1.

Cutoff Dates for Safety Data Presented in Summary of Clinical Safety

Phase/Study

Safety Data Available (Through)Phase 3
(StudyC4591001)

Reactogenicity: up to 7 days after
each dose

N (number
randomized)
9839c

Blinded AEs/SAEs:
 1 month post-dose 2(including HIV positive
subset) up to unblinding date(including HIV positive
subset)d43,847

Open-label AEs/SAEs (participantsoriginally randomized to BNT162b2):
 Date of unblinding to data
cutoff

20,309Blinded and open-label AEs/SAEs
 BNT162b2 participants withat least 6 months follow-up
post-dose 2

12,006Age(years of age)
Younger: 16 to 55
Older: >55

Data Cutoff
Date
13 Mar 2021

19,525Open-label AEs/SAEs (participantsoriginally randomized to placebo but
were vaccinated with BNT162b2 after
treatment disclosure): Date of BNT162b2
vaccination (after treatment
disclosure) to data cutoff
a. Adverse event results beyond 7 days after Dose 2, as defined in the protocol objectives, are included inPhase 3 analyses.
b. The 360 Phase 2 participants are included in the Phase 3 analyses.
c. This subset of 9839 participants (which includes Phase 2 participants) completed the e-diary forreporting local reactions and systemic events.
d. Up to ~6 months after Dose 2

2.7.4.1. Exposure to BNT162b2
2.7.4.1.1. Overall Safety Evaluation Plan and Narratives of Safety Studies
The overall safety evaluation plan for Study BNT162-01 is presented in Section 2.7.4.1.1.1.
The overall safety evaluation plan for Study C4591001 is presented in Section 2.7.4.1.1.2.
Study BNT162-01 and Study C4591001 use different designs and safety data collection
methods and definitions. For these reasons, safety data from Study BNT162-01 andStudy C4591001 will not be pooled for analysis. As BNT162b1 and BNT162b2 were the 2
vaccine candidates evaluated in Phase 1 of the C4591001 study, only these 2 constructs will
be discussed in the SCS as it relates to how the final candidate and dose level was
determined.

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2.7.4.1.1.1. Phase 1/2 Study BNT162-01
Safety and immunogenicity data from Study BNT162-01 are summarized in this BLA in
support of the larger dataset from Phase 1/2/3 registration Study C4591001.
2.7.4.1.1.1.1. Safety Objectives and Endpoints (Study BNT162-01)
The safety objectives and endpoints for Study BNT162-01 are presented in Table 2.
Table 2.

Safety Objectives and Endpoints for Study BNT162-01a

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Objective
Primary:
To describe the safety and tolerability profiles ofprophylactic BNT162 vaccines in healthy adults
after single dose (prime only) or P/B immunization.

a.

Endpoint

Solicited local reactions at the injection site
(pain, tenderness, erythema/redness,
induration/swelling) recorded up to 7±1 day
after each immunization.
 Solicited systemic reactions (nausea, vomiting,diarrhea, headache, fatigue, myalgia, arthralgia,
chills, loss of appetite, malaise, and fever)recorded up to 7±1 day after each
immunization.
 The proportion of subjects with at least 1
unsolicited TEAE: For BNT162a1, BNT162b1, BNT162b2,
and BNT162c2 (P/B): occurring up to
21±2 d after the prime immunization and
28±4 d after the boost immunization.
 For BNT162c2 (single dose): The
proportion of subjects with at least 1
unsolicited TEAE occurring up to 28±4
days after the immunization.
Only BNT162b1 and BNT162b2 are discussed in this SCS.

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2.7.4.1.1.1.2. Overall Design (Study BNT162-01)
Details regarding the study design of Study BNT162-01 are presented in the study protocol(Module 5.3.5.1 BNT162-01 Protocol Section 4).
German Study BNT162-01 is the ongoing, FIH, Phase 1/2 dose level-finding study, in which
healthy adults aged 18 to 55 or 56 to 85 all receive active vaccine (open-label andnon-randomized). Four vaccine candidates from 3 different RNA platforms are being tested.
The trial has two parts: a dose-finding part (Part A) and a part dedicated to recruiting
expansion cohorts with dose levels which were selected from data generated in Part A(Part B). The study schema for Part A is presented in Appendix A (Section 2.7.4.6.1).
BNT162b1 and BNT162b2 were administered in a prime/boost two-dose regimen separated
by approximately 21 days:


BNT162b1 (dose levels: 1, 3, 10, 20, 30, 50, 60 µg)



BNT162b2 (dose levels: 1, 3, 10, 20, 30 µg).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The safety review committee (SRC) recommended that a second dose of BNT162b1 at the
60 µg dose level not be administered due to the reactogenicity after the first dose.
Subject safety was to be monitored from Visit 0 (screening) until approximately 6 months
after the last immunization.
The following data are summarized and presented in this SCS as primary endpoints:


Local reactions and systemic event data (acquired through the subject paper diaries)
through Visit 5 (up to 7 days post-dose 2)

TEAEs through Visit 7 (1-month follow-up visit post-dose 2)

Complete details regarding planned time points for all safety assessments during Phase 2/3
are provided in the SoA in Appendix A (Section 2.7.4.6.1).
2.7.4.1.1.1.3. Study Population (Study BNT162-01)
The full eligibility criteria for Study BNT162-01 can be found in the protocol(Module 5.3.5.1 BNT162-01 Protocol Section 5.1.1 and 5.2.1).
The study enrolled healthy adults 18 to 85 years of age. Healthy participants with preexisting
stable disease, defined as disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks prior to enrollment, were eligible
for the study. Individuals with certain medical conditions that could affect participant safety
or evaluation of vaccine safety or immunogenicity were excluded. A complete list ofinclusion and exclusion criteria is available in the protocol (Module 5.3.5.1 BNT162-01
Protocol Section 5).

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2.7.4.1.1.1.4. Analysis Sets (Study BNT162-01)
Populations from Study BNT162-01 discussed in this SCS include the following:
Population

Screened Set
Safety Set (SAF)

Description

The screened set is defined as all subjects who signed informed consent
The safety set is defined as all subjects who received at least one dose of study
intervention

2.7.4.1.1.1.5. Safety Assessments (Study BNT162-01)
Details regarding safety assessments for Study BNT162-01 are found in Module 5.3.5.1
BNT162-01 Protocol Section 8.2.

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Safety assessments were collected at planned time points as described in the Schedule ofActivities (Appendix A, Section 2.7.4.6.1.2). Key Safety Assessments included:
Physical examinations, Vital Signs, ECGs

Clinical laboratory tests were performed at the times defined in the SoA and thespecific tests are presented in Module 5.3.5.1 BNT162-01 Protocol Section 10.2. The
classification of laboratory tests is presented in Module 5.3.5.1 BNT162-01 Statistical
Analysis Plan Section 6.7.2.

Local reactions after IM immunization were assessed by the investigator at the times
given in the SoA (Appendix A, Section 2.7.4.6.1.2). In the 7 days after administrationof the study intervention, participants used subject diaries to record any reactions
between visits: solicited local reactions at the injection site and solicited systemic
reactions (see Appendix A [Section 2.7.4.6.1.3.2] for further details). Grading scales
used in this study to assess local reactions and systemic events are derived from the
FDA CBER guidelines on toxicity grading scales for healthy adult volunteers
enrolled in preventive vaccine clinical trials.1



SARS-CoV-2 testing (PCR-based and antibody-based). This includes PCR-based
testing for SARS-CoV-2 as an eligibility criterion and blood draws foranti-SARS-CoV-2 antibody testing as baseline reference for immunogenicity
analysis. If required, this reference will allow the discrimination between vaccinatedand infected subjects.

AEs and SAEs were collected, recorded, and reported as defined in Module 5.3.5.1
BNT162-01 Protocol Section 8.3 and further discussed in Appendix A(Section 2.7.4.6.1.3.3).



AESI were considered to be enhanced respiratory disease or flu-like symptomatologythat did not resolve after 7 days or with symptom kinetics that are inconsistent with arelationship to RNA immunization.

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2.7.4.1.1.1.6. Statistical Methods (Study BNT162-01)
There is no hypothesis testing in Study BNT162-01. Statistical methods are described in the
study protocol (Module 5.3.5.1 BNT162-01 Protocol Section 9.4) and in the SAP (Module
5.3.5.1 BNT162-01 SAP).
In general, data will be summarized by groups and groups may be combined as appropriate.
Part A and Part B will be analyzed separately and may be combined as appropriate.
All AEs will be coded using MedDRA terms. TEAEs will be summarized using the safety set(SAF). In general, AEs will be analyzed by group (ie, by type and dose level) and for each
immunization. Additionally, AEs will be summarized for all dose levels combined for each
type. For each analysis, the number and percentage of subjects reporting at least one AE will
be summarized by PT nested within SOC for each AE type. The number and percentage ofsubjects with any AE will be summarized by worst grade by PT nested within SOC.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)For each immunization, the number and percentage of subjects reporting at least one local
reaction or systemic reaction (ie, solicited data collected using subject diaries) will besummarized for any local reactions or systemic reactions and for Grade ≥3 local reactions or
systemic reactions in the SAF.
The analysis of local and systemic reactions will be repeated with a reduced set of terms(called the “comparability analysis”), to facilitate like-for-like comparisons between different
trials in the clinical development program for BNT162 vaccines. The number and percentage
of subjects reporting at least one local reaction will be summarized by worst grade using the
SAF.
Safety data other than AEs that will be summarized includes clinical laboratory parameters,
vital signs, and ECGs. All safety analyses will be based on the safety set and will besummarized descriptively by group unless otherwise stated.
Clinical laboratory parameters at each timepoint and change from baseline to each postbaseline time point will be summarized using descriptive summary statistics for eachparameter by group.
The occurrence of clinically significant abnormal laboratory results within a study subject
will be analyzed using descriptive summary statistics for each parameter and visit by group.
Abnormal laboratory results will be graded using criteria based on the guidance given in the
FDA CBER guidelines on toxicity grading scales for healthy adult volunteers enrolled inpreventive vaccine clinical trials.1
2.7.4.1.1.2. Pivotal Phase 1/2/3 Safety, Immunogenicity, and Efficacy Study C4591001
2.7.4.1.1.2.1. Safety Objectives, Estimands, Endpoints (Study C4591001)
Safety objectives, estimands, and endpoints for Study C4591001 are presented in Table 3.

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Table 3.

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Primary:

Safety Objectives, Estimands, and Endpoints for Study C4591001
Objectivesa

To describe the safety and tolerability
profiles of prophylactic BNT162
vaccines in healthy adults after 1 or 2
doses

To describe the safety profile of a third
dose of prophylactic BNT162b2
administered to healthy adults 6 to 12
months after the second dose of either
BNT162b1 or BNT162b2

Primary:

Estimands

Endpoints

Primary:
PHASE 1
In participants receiving at least 1 dose of 
Local reactions (pain at the injection
study intervention, the percentage ofsite, redness, and swelling)
participants reporting:
Systemic events (fever, fatigue,
Local reactions for up to 7 days
headache, chills, vomiting, diarrhea,
following each dose
new or worsened muscle pain, and
Systemic events for up to 7 days
new or worsened joint pain)
following each doseAEs
AEs from Dose 1 to 1 month afterSAEs
the last dose
SAEs from Dose 1 to 6 months after
the last doseIn addition, the percentage of participantswith:
Abnormal hematology andchemistry laboratory values 1 and 7
days after Dose 1; and 7 days after
Dose 2Grading shifts in hematology andchemistry laboratory assessments
between baseline and 1 and 7 days
after Dose 1; and before Dose 2 and7 days after Dose 2

Hematology and chemistry laboratory
parameters detailed in Module 5.3.5.1
C4591001 Protocol Section 10.2.

In participants receiving a third dose of
BNT162b2, the percentage of participants
reporting:
Local reactions for up to 7 days after
Dose 3
Systemic events for up to 7 days
after Dose 3

AEs and SAEs from Dose 3 to
1 month after Dose 3

Exploratory

Local reactions (pain at the injection
site, redness, and swelling)
Systemic events (fever, fatigue,headache, chills, vomiting, diarrhea,
new or worsened muscle pain, andnew or worsened joint pain)
AEs
SAEs

Reference
Interim data for local reactions andsystemic events reported up to 7 days after
each dose, and AEs and SAEs are reported
from Dose 1 to 1 month after the last dose
for all groups evaluated, and to the cutoff
date after Dose 2 for the BNT162b2 30 µggroup only in final analysis interim CSR
dated 03 December 2020.
AEs and SAEs from Dose 1 to theunblinding date for the BNT162b2 30 µggroup only are reported in this CSR.
Interim data are reported in final analysis
interim CSR dated 03 December 2020.

Data will be reported at a later time.

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Table 3.

Safety Objectives, Estimands, and Endpoints for Study C4591001

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Objectivesa
To define the safety profile ofprophylactic BNT162b2 in the first 360
participants randomized (Phase 2)

To define the safety profile ofprophylactic BNT162b2 in allparticipants randomized in Phase 2/3

To define the safety profile ofprophylactic BNT162b2 in participants
12 to 15 years of age in Phase 3

Estimands

PHASE 2/3

Endpoints

Primary Safety
In participants receiving at least 1 dose of 
Local reactions (pain at the injection
study intervention, the percentage ofsite, redness, and swelling)
participants reporting:
Systemic events (fever, fatigue,
Local reactions for up to 7 days
headache, chills, vomiting, diarrhea,
following each dose
new or worsened muscle pain, andnew or worsened joint pain)Systemic events for up to 7 days
following each doseAEs
AEs from Dose 1 to 7 days after theSAEs
second dose
SAEs from Dose 1 to 7 days after
the second dose
In participants receiving at least 1 dose of AEsstudy intervention, the percentage ofSAEs
participants reporting:In a subset of at least 6000

Local reactions for up to 7 days
participants:
following each doseo Local reactions (pain at the
Systemic events for up to 7 days
injection site, redness, andfollowing each doseswelling)AEs from Dose 1 to 1 month aftero Systemic events (fever, fatigue,
the second dose
headache, chills, vomiting,diarrhea, new or worsenedSAEs from Dose 1 to 6 months after
muscle pain, and new or
the second doseworsened joint pain)
In participants receiving at least 1 dose of 
Local reactions (pain at the injection
study intervention, the percentage ofsite, redness, and swelling)
participants reporting:
Systemic events (fever, fatigue,
Local reactions for up to 7 days
headache, chills, vomiting, diarrhea,
following each dose
new or worsened muscle pain, and
Systemic events for up to 7 days
new or worsened joint pain)
following each doseAEs
AEs from Dose 1 to 1 month afterSAEs
the second dose
SAEs from Dose 1 to 6 months after
the second dose

Reference
Interim data are reported in final analysis
interim CSR dated 03 December 2020.

Interim data are reported up to 1 monthafter Dose 2 and to the data cutoff date
(14 November 2020) in final analysis
interim CSR dated 03 December 2020.
Cumulative interim data up to cutoff date
are reported in this CSR.

Data will be reported separately.

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Table 3.

Safety Objectives, Estimands, and Endpoints for Study C4591001

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Objectivesa

To describe the safety and tolerability
profile of BNT162b2SA given as 1 or 2
doses to BNT162b2-experienced
participants, or as 2 doses to BNT162b2naïve participants
To describe the safety and tolerability
profile of BNT162b2 given as a third
dose to BNT162b2-experienced
participants

To describe the safety, immunogenicity,and efficacy of prophylactic BNT162b2
in individuals with confirmed stable HIV
diseaseTo describe the safety andimmunogenicity of prophylactic
BNT162b2 in individuals 16 to 55 yearsof age vaccinated with study intervention
produced by manufacturing “Process 1”
or “Process 2”b

Estimands

In participants receiving at least 1 dose of
study intervention, the percentage ofparticipants reporting: Local reactions for up to 7 days
following each dose
 Systemic events for up to 7 days
following each dose AEs from Dose 1 to 1 month after thesecond dose
 SAEs from Dose 1 to 5 or 6 months
after the second dose







Endpoints

Local reactions (pain at the injection
site, redness, and swelling)
Systemic events (fever, fatigue,headache, chills, vomiting, diarrhea,
new or worsened muscle pain, andnew or worsened joint pain)
AEs
SAEs

Exploratory

Reference

Data will be reported at a later time.

All safety, immunogenicity, and efficacy
endpoints described above

Safety data only in participants withconfirmed stable HIV disease arereported in this CSR.

AEs
SAEs
SARS-CoV-2 neutralizing titers

Data will be reported at a later time.



a. HIV-positive participants in Phase 3 will not be included in analyses of the objectives, with the exception of the specific exploratory objective.
b. See Module 5.3.5.1 C4591001 Protocol Section 6.1.1 for a description of the manufacturing process. The safety results for individuals 16 to 55 years ofage vaccinated with study intervention produced by manufacturing “Process 1” or “Process 2” will be summarized descriptively when data become available.

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2.7.4.1.1.2.2. Overall Design (Study C4591001)
US Study C4591001 is the ongoing, randomized, placebo-controlled, observer-blind, Phase
1/2/3 pivotal registration study. The study consists of 2 parts:
1. Phase 1: to identify preferred vaccine candidate(s) and dose level(s);2. Phase 2/3: an expanded cohort and efficacy part.
These parts, and the progression between them, are detailed in the schema presented inAppendix B (Section 2.7.4.6.2.1).
Study C4591001 was conducted at sites in the US, Brazil, Argentina, Turkey, South Africa,and Germany

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Phase 1In Phase 1, 13 groups were studied, corresponding to a total of 195 participants. Each group(vaccine candidate/dose level/age group) was comprised of 15 participants randomized 4:1 toreceive active vaccine or placebo (12 participants randomized to active vaccine and 3 toplacebo, such that the placebo participants across the groups would produce a roughly
comparably-sized cohort). Study intervention was to be administered intramuscularly into
the deltoid muscle, preferably of the nondominant arm to 2 age cohorts (18 to 55 and 65 to
85 years of age,) in a two-dose regimen separated by 21 days at the following dose levels:


BNT162b1 (dose levels: 10, 20, 30, 100 µg)
BNT162b2 (dose levels: 10, 20, 30 µg).

The Internal Review Committee (IRC) recommended that a second dose of BNT162b1 at
100 µg not be administered due to reactogenicity after the first dose in the younger age
group. Participants in this group of younger adults instead received a second dose of
BNT162b1 at the 10 µg dose level.
Participants received active vaccine or placebo at Visit 1, with next day and 1-week followup visits (Visits 2 and 3) post-dose 1. Participants received dose 2 at Visit 4 (19 to 23 days
after Visit 1). Follow-up visits were scheduled at 1-week, 2-weeks, 1-month, 6-months, 12months- and 24-months.
Participants who originally received placebo may have become eligible for receipt of
BNT162b2 or another COVID-19 vaccine.
Phase 1 participants who originally received BNT162b1 or BNT162b2 at dose levels of
10, 20, or 30 µg at Doses 1 and 2 were offered an additional dose of BNT162b2 at 30 µg
approximately 6 to 12 months after their second dose of BNT162. This would provide an
early assessment of the safety of a third dose of BNT162, as well as its immunogenicity. The
booster analyses will be reported at a later time.
Participants were expected to participate for up to a maximum of approximately 26 months.
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All participants in Phase 1 recorded local reactions, systemic events, and antipyretic/pain
medication usage for 7 days, each evening following administration of study intervention
using an e-diary. This allowed recording of these assessments only within a fixed time
window, thus providing the accurate representation of the participant’s experience at thattime.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The following data are summarized and presented in this SCS as Phase 1 safety endpoints:


Local reactions and systemic event data (acquired through the e-diaries) for up to 7
days after Dose 1 and Dose 2



AEs through Visit 7 (1-month follow-up visit post-dose 2) and SAEs through the data
cutoff date of 24 August 2020 (safety results for BNT162b1 at the 100 µg dose levelin the younger age group are presented up to 3 weeks after Dose 1 or to before Dose 2
based on the data cutoff date).

Long-term follow-up (approximately 6 months after Dose 2 [as of cutoff date
13 March 2021]) of AEs and SAEs for Phase 1 participants who were randomized toreceive BNT162b2 30 µg or control.

Abnormal hematology and chemistry laboratory values, as well as grading shifts inhematology and chemistry laboratory assessments, through Visit 5 (7 days postdose 2).

Complete details regarding planned time points for all safety assessments during Phase 1 areprovided in the SoA in Appendix B (Section 2.7.4.6.2.2.1). The investigator may havescheduled visits (unplanned visits) in addition to those listed in the SoA table in order to
conduct evaluations or assessments required to protect the well-being of the participant.
Safety assessments for Study C4591001 are detailed in Section 2.7.4.1.1.2.5 and 2.7.4.6.2.3.
The Sponsor/agent study team was not blinded in this part of the study. Participants enrolled
in Phase 1 were followed for cases of COVID-19 but did not contribute to the overall
efficacy assessment. Details regarding efficacy and immunogenicity methods, results, andconclusions are presented in the SCE (Module 2.7.3).
Based upon review of safety and immunogenicity from the Phase 1 part of the study, a final
candidate and dose level of 30 µg BNT162b2 was selected.
Phase 2/3
BNT162b2 at the 30 µg dose level was the vaccine candidate chosen by Pfizer/BioNTech toproceed into Phase 2/3. Participants ≥12 years of age (stratified as 12-15, 16-55 or >55 yearsof age, with the intention that a minimum of 40% of participants would be in the >55-year
stratum) were randomized 1:1 to receive vaccine or placebo. The Phase 2 part of the study
evaluated safety and immunogenicity for the first 360 participants enrolled (180 to active
vaccine and 180 to placebo) in order to confirm the safety profile of BNT162b2 as seen in
Phase 1. Participants enrolled into Phase 2 contributed to the overall efficacy assessment.
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It was planned for the Phase 2/3 part of the study to comprise of approximately 21,999
vaccine recipients per group, for a total sample size of 43,998. The 12- to 15-year stratum
will be comprised of up to approximately 2000 participants (1000 vaccine recipients)
enrolled at selected investigational sites.
Participants received active vaccine or placebo at Visit 1 (dose 1) and Visit 2 (dose 2, 19 to
23 days after Visit 1). Follow-up visits were scheduled at 1-month, 6-months, 12-monthsand 24-months (as described in the SoA, Appendix B, Section 2.7.4.6.2.2.2).
Participants ≥16 years of age who originally received placebo and became eligible for receiptof BNT162b2 according to recommendations detailed separately, had the opportunity toreceive BNT162b2 in a phased manner as part of the study (no later than 6 months after
Vaccination 2 [at the time of the originally planned Visit 4]). The investigator ensured thatthe participant met at least 1 of the recommendation criteria. Any participant ≥16 years ofage who originally received placebo but then went on to receive BNT162b2 moved to a new
visit schedule (2.7.4.6.2.2.3) and received 1 dose of BNT162b2 at each additional
vaccination visit (Visits 101 and 102, receiving Dose 3 and Dose 4, respectively).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The following data are summarized and presented in this SCS as Phase 2/3 safety endpoints:


For Phase 2 (first 360 participants), reactogenicity results for up to 7 days after Dose
1 and Dose 2, AEs and SAEs through the data cutoff date (2 September 2020), which
includes up to 7 days follow-up after Dose 2.



For Phase 3, reactogenicity results for up to 7 days after Dose 1 and Dose 2, AEs andSAEs through the data cutoff date (13 March 2021), which includes up to 6 months
follow-up after Dose 2 (see Section 2.7.4.2.4.2 for more details).

Complete details regarding planned time points for all safety assessments during Phase 2/3
are provided in the SoA in Appendix B (Section 2.7.4.6.2.2.2). An unplanned potential
COVID-19 illness visit and unplanned potential COVID-19 convalescent visit were required
at any time between Visit 1 and Visit 6 (24-month follow-up visit) that potential COVID-19
symptoms were reported, including MIS-C.
Prior infection with SARS-CoV-2 was assessed at baseline and evaluated per serologicalsamples over 24 months to explore efficacy against asymptomatic SARS-CoV-2 infections
and to ensure safety in both sero-negative and sero-positive participants. Safety assessments
for Study C4591001 are detailed in Section 2.7.4.1.1.2.5 and 2.7.4.6.2.3.
Planned Analyses
The following analyses are not included in this report and will be reported at a later time:For evaluation of boostability, a subset of Phase 3 participants 18 to 55 years of age
will receive a third dose of BNT162b2 or a third and potentially a fourth dose of
prototype BNT162b2VOC (based upon the South African variant and hereafter referred
to as BNT162b2SA). The third dose of BNT162b2 or BNT162b2SA will beadministered approximately 5 to 7 months after their second dose of BNT162 (atCONFIDENTIAL
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Visit 301) and a subset of those participants who received the third dose of
BNT162b2SA will receive a further dose of BNT162b2SA one month after Dose 1 of
BNT162b2SA (at Visit 303).


To further describe potential homologous and heterologous protection against
emerging SARS-CoV-2 VOCs, a new cohort of participants will be enrolled who are
COVID-19 vaccine-naïve (ie, BNT162b2-naïve) and have not experienced
COVID-19. They will receive BNT162b2SA given as a 2-dose series, separated by
21 days.

2.7.4.1.1.2.3. Study Population (Study C4591001)
The full eligibility criteria for Study C4591001 can be found in the protocol (Module 5.3.5.1
C4591001 Protocol Section 5).
The following eligibility criteria were designed to select participants for whom participationin the study was considered appropriate.

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Key inclusion criteria:
Participants were eligible to be included in the study only if all of the following criteria
apply:


Male or female participants in the following age groups:
o Phase 1: Between the ages of 18 and 55 years, inclusive, and between 65 and85 years, inclusive, at randomizationo Phase 2/3: ≥12 years, at randomization



Healthy participants as determined by medical history, physical examination (ifrequired), and clinical judgment of the investigator to be eligible for inclusion in the
study
Note: Healthy participants with preexisting stable disease, defined as disease notrequiring significant change in therapy or hospitalization for worsening diseaseduring the 6 weeks before enrollment, could be included. Specific criteria for Phase 3
participants with known stable infection with HIV, HCV, or HBV can be found in
Module 5.3.5.1 C4591001 Protocol Section 10.8.

Phase 2/3 only: Participants who, in the judgment of the investigator, were at higher
risk for acquiring COVID-19 (including, but not limited to, use of mass transportation,
relevant demographics, and frontline essential workers).

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Key exclusion criteria:

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Participants were excluded from the study if any of the following criteria applied:

Other medical or psychiatric condition including recent (within the past year) or
active suicidal ideation/behavior or laboratory abnormality that may increase the riskof study participation or, in the investigator’s judgment, make the participant
inappropriate for the study.

Phases 1 and 2 only: Known infection with HIV, HCV, or HBV.

History of severe adverse reaction associated with a vaccine and/or severe allergic
reaction (eg, anaphylaxis) to any component of the study intervention(s).

Receipt of medications intended to prevent COVID 19.

Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2
NAAT result was not available) or microbiological (based on COVID-19
symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID 19.



Phase 1 only: Individuals at high risk for severe COVID-19, including those with anyof the following risk factors:
 Hypertension
 Diabetes mellitus
 Chronic pulmonary disease Asthma Current vaping or smoking
 History of chronic smoking within the prior year Chronic liver disease Stage 3 or worse chronic kidney disease (glomerular filtration rate
<60 mL/min/1.73 m2)
 Resident in a long-term facility
 BMI >30 kg/m2
 Anticipating the need for immunosuppressive treatment within the next 6 months

 Phase 1 only: Individuals currently working in occupations with high risk of
exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel).
 Immunocompromised individuals with known or suspected immunodeficiency, as
determined by history and/or laboratory/physical examination.

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2.7.4 Summary of Clinical Safety Phase 1 only: Individuals with a history of autoimmune disease or an active
autoimmune disease requiring therapeutic intervention, including but not limited to:systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid
arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren’s syndrome, idiopathic
thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cellarteritis (temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus(type 1).
 Bleeding diathesis or condition associated with prolonged bleeding that would, in theopinion of the investigator, contraindicate intramuscular injection.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT) Women who are pregnant or breastfeeding.
Previous vaccination with any coronavirus vaccine.

Individuals who receive treatment with immunosuppressive therapy.

Phase 1 only: Regular receipt of inhaled/nebulized corticosteroids.

Receipt of blood/plasma products or immunoglobulin, from 60 days before study
intervention administration or planned receipt throughout the study.

Participation in other studies involving study intervention within 28 days prior to
study entry through and including 6 months after the last dose of study intervention,with the exception of interventional studies for prevention of COVID 19, which areprohibited throughout study participation.

Previous participation in other studies involving study intervention containing lipid
nanoparticles.

For Phase 1 only:o Positive serological test for SARS-CoV-2 IgM and/or IgG antibodies at thescreening visit.
o Any screening hematology and/or blood chemistry laboratory value that meetsthe definition of a ≥ Grade 1 abnormality.
o Positive test for HIV, HBsAg, HBc Abs, or HCV Abs at the screening visit.
o SARS-CoV-2 NAAT-positive nasal swab within 24 hours before receipt ofstudy intervention.

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2.7.4.1.1.2.4. Analysis Sets (Study C4591001)
Populations discussed in this SCS include the following:
Population
Enrolled
Randomized
SafetyDescription
All participants who had a signed ICD
All participants who were assigned a randomization number in the IWR
systemAll randomized participants who received at least 1 dose of the study
intervention.
Analyses of reactogenicity endpoints will be based on a subset of thesafety population that includes participants with any e-diary datareported after vaccination.

2.7.4.1.1.2.5. Safety Assessments (Study C4591001)

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Safety assessments were collected at planned time points as described in Appendix B(Section 2.7.4.6.2). Key safety assessments included:

A clinical assessment, including medical history, was performed on all participants at
his/her first visit to establish a baseline. Significant medical history and observations
from any physical examination, if performed, were documented in the CRF.

The safety parameters included reactogenicity e-diary reports of local reactions andsystemic events, fever, and use of antipyretic medication that occurred in the 7 days
after administration of the study intervention in a subset of participants (seeAppendix B [Section 2.7.4.6.2.3.1] for further details). Grading scales used in thisstudy to assess local reactions and systemic events were derived from the FDA CBER
guidelines on toxicity grading scales for healthy adult volunteers enrolled inpreventive vaccine clinical trials.1



AEs and SAEs were collected, recorded, and reported as defined in Module 5.3.5.1
C4591001 Protocol Section 8.3 and further discussed below in Appendix B (Section
2.7.4.6.2.3.2).

Acute reactions within the first 4 hours after administration of the study intervention(for the first 5 participants vaccinated in each Phase 1 group), and within the first 30
minutes (for the remainder of participants), were assessed and documented in the AE
CRF.



Safety subgroup analyses by age, country, ethnicity, sex, and race were performed.

Targeted medical events of potential clinical interest by PT, HLT, or SMQ (fullscope, including broad and narrow) were monitored.

Participants in all phases of the study were surveilled for potential COVID-19 illness
from Visit 1 onwards. Further details are in Appendix B (Section 2.7.4.6.2.3.4). Note
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2.7.4 Summary of Clinical Safetythat while this was monitored throughout the study, analyses were only planned forPhase 2/3 as efficacy endpoints.


For Phase 1, safety laboratory tests were performed at the times defined in the SoA(Appendix B [Section 2.7.4.6.2.2.1]). The specific tests are presented in the Statistical
Analysis Plan (Module 5.3.5.1 C4591001 Statistical Analysis Plan Section 3.1.1.6)
and further described in Module 5.3.5.1 C4591001 Protocol Section 8.2.1. The
primary criterion for abnormality followed the Pfizer safety rule book.



For Phase 1, a physical examination was performed. It evaluated any clinicallysignificant abnormalities within the following body systems: general appearance;
skin; head, eyes, ears, nose, and throat; heart; lungs; abdomen; musculoskeletal;
extremities; neurological; and lymph nodes. Clinically significant abnormal results
were recorded in the CRF.

No adverse events of special interest were defined for Study C4591001; however, targeted
medical events were monitored throughout the study.

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2.7.4.1.1.2.6. Statistical Methods (Study C4591001)
Statistical methods are described in the study protocol (Module 5.3.5.1 C4591001 Protocol
Section 9.4) and in the statistical analysis plan (Module 5.3.5.1 C4591001 Statistical
Analysis Plan)
Safety objectives were evaluated by descriptive summary statistics for local reactions andsystemic events, AEs/SAEs, and abnormal hematology and chemistry laboratory parameters(Phase 1 only) for each vaccine group. A 3-tier approach was used to summarize AEs in
Phase 2/3. Under this approach, AEs were classified into 1 of 3 tiers:
Tier 1 events: prespecified events of clinical importance, identified in the product’s
safety review plan; there are no Tier 1 AEs identified for this program.
Tier 2 events: those that are not Tier 1 but are considered “relatively common”; a
MedDRA preferred term is defined as a Tier 2 event if there are at least 1% ofparticipants in at least 1 vaccine group reporting the event; andTier 3 events: those that are neither Tier 1 nor Tier 2 events.
For Tier 2 events, 2-sided 95% CIs for the difference between the vaccine and placebogroups in the percentage of participants reporting the events based on the Miettinen andNurminen method will be provided.2 For Tier 3 events, counts and percentages for eachvaccine group will be provided. The safety analyses are based on the safety population.
Analyses of reactogenicity endpoints are based on a subset of the safety population that
includes participants with any e-diary data reported after vaccination. Participants will besummarized by vaccine group according to the study interventions they actually received.
Missing reactogenicity e-diary data will not be imputed; missing AE dates will be handledaccording to the Pfizer safety rules.

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AEs and SAEs reported during the open-label follow-up period will be summarized
separately for participants who were unblinded at the time of being eligible for receipt of
BNT162b2 according to recommendations detailed separately, and available in the electronic
study reference portal, or no later than at approximately Visit 4.
AE analyses of participants who had different durations of follow-up time due to unblinding
in the study (per protocol) were summarized as incidence rates (IR) adjusted for exposure
time. This was calculated as: (number of participants reporting event) / (total exposure time
across all participants in the specified group). This accounts for variable exposure since
unblinding began for individual participants. Two-sided 95% CIs for the IRs were provided
based on Poisson distribution.
Planned Analyses
For Phase 3 participants enrolled for assessment of boostability and protection against
emerging VOCs, descriptive summary statistics will be provided at a later time.
2.7.4.1.1.3. Narratives

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Narrative summaries were written for the following participants in Study BNT162-01:
Participants who died;Participants who experienced SAEs assessed as related to study intervention by theinvestigator;

Participants with any AEs leading to withdrawal from the studyParticipants with COVID-19

These participant narratives are available in Module 5.3.5.1 BNT162-01 CSR Section 12.6.
Narrative summaries were written for the following participants in Study C4591001:


Deaths, vaccine-related SAEs, all other SAEs, safety-related withdrawals

AEs of interest requested by FDA: anaphylaxis, Bell’s palsy, lymphadenopathy,
appendicitis, and pregnancy exposures and outcomes

AESIs with a numerical imbalance with a higher frequency (or incidence rate) in thevaccine group vs placebo group that led to withdrawal, were related, or had biologicalplausibility



COVID-19 cases (participants with severe and/or multiple episodes).

These participant narratives are available in Module 5.3.5.1 C4591001 Efficacy Final
Analysis Interim CSR Section 14 Subject Narratives (for data available as of the

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14 November 2020 cutoff date) or Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Section 14 Subject Narratives (for data available as of the 13 March 2021 cutoff date)
2.7.4.1.2. Overall Extent of Exposure, Disposition, and Study Population
Characteristics
2.7.4.1.2.1. Study BNT162-01
Study results presented below are for Part A through the data cutoff date of 23 October 2020and may not be representative of the final data. The full interim CSR for Study BNT162-01
is provided in Module 5.3.5.1 BNT162-01 CSR.

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2.7.4.1.2.1.1. Disposition (Phase 1, Study BNT162-01)
In the BNT162b1 younger age group, a total of 84 participants were enrolled, with
12 participants in each dose group (1 µg, 3 µg, 10 µg, 20, µg, 30 µg, 50 µg, and 60 µg dosegroups) (note: 60 µg group received only Dose 1 per SRC decision due to Dose 1
reactogenicity). In the BNT162b1 older age group, a total of 36 participants were enrolled,with 12 participants in each dose group (10 µg, 20, µg, 30 µg dose groups) (note: 10 µggroup had data to 1 month after Dose 2; 20 and 30 µg groups had available data to 7 days
after Dose 2). 80/84 younger and 11/36 older participants in the BNT162b1 group completed
the study (ie, through the end of treatment visit), and 4 premature discontinuations haveoccurred (none in the 30 µg dose group or the older participant age group).
In the BNT162b2 younger age group, a total of 60 participants were enrolled, with
12 participants in each dose group (1 µg, 3 µg, 10 µg, 20, µg, and 30 µg groups). In the
BNT162b2 older age group, a total of 36 participants were enrolled, with 12 participants ineach dose group (10 µg, 20, µg, 30 µg dose groups). 53/60 younger and 30/36 older
participants in the BNT162b2 group completed the study (ie, through end of treatment visit).
Two premature discontinuations have occurred (none in the 30 µg dose group or the older
participant age group).
2.7.4.1.2.1.2. Exposure (Phase 1, Study BNT162-01)
For BNT162b1, dosing of participants in the younger age group with the second 60 µg
BNT162b1 dose was not performed. After 12 participants had received Dose 1, the SRC
decided not to administer Dose 2 to these participants. 95.8% (69/72) of participants in allother dose levels received Dose 2. In the BNT162b1 older age group, 97.2% (35/36) ofparticipants in all dose levels received Dose 2.
For the BNT162b2 group, 96.7% (58/60) and 100% (36/36) of participants in the younger
and older age groups, respectively (in all dose levels) received Dose 2.
2.7.4.1.2.1.3. Safety Data Sets Analyzed (Phase 1, Study BNT162-01)
For BNT162b1 and BNT162b2, all participants randomized to receive study intervention in
the younger and older age groups were included in the SAF.

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2.7.4.1.2.1.4. Demographic and Other Characteristics of Study Population (Phase 1,
Study BNT162-01)
In the BNT162b1 younger age group, BNT162b1 was administered to 84 participants, amongwhom 52% were male and 48% were female, 96% were White and 2% wereHispanic/Latino, with a median 36 years of age. In the BNT162b1 older age group (56 to 85
years of age), BNT162b1 was administered to 36 participants, among whom 36% were maleand 64% were female, all were White and none were Hispanic/Latino, with a median 67
years of age.
In the BNT162b2 younger age group, BNT162b2 was administered to 60 participants, amongwhom 43% were male and 57% were female, 100% were White, none were Hispanic/Latino,with a median 42 years of age. In the BNT62b2 older age group, BNT162b2 wasadministered to 36 participants, among whom 50% were male and 50% were female, 100%
were White, none were Hispanic/Latino, with a median 65 years of age.
Baseline Medical History

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Participants in both the BNT162b1 and BNT162b1 groups were healthy with a medical
history profile consistent with that of a healthy general population in the younger age group.
2.7.4.1.2.1.5. Diary Compliance (Phase 1, Study BNT162-01)
For BNT162b1 and BNT162b2, the participant’s diary compliance for reporting
reactogenicity was ≥99% 0 to 6 days after Dose 1. The participant’s diary compliance forreporting reactogenicity was ≥64% and ≥92% from 0 to 6 days after Dose 2 for BNT162b1
and BNT162b2, respectively.
Overall, lower percentages postdose 2 were due to the ongoing nature of the study. These
results are as of the data cutoff date and may not be representative of the final data.
2.7.4.1.2.2. Phase 1 (Study C4591001)
Results for healthy adults 18 to 85 years of age (younger age group: 18 to 55; older age
group: 65 to 85) in the Phase 1 portion of Study C4591001 are presented through the data
cutoff date of 24 August 2020. Updated disposition is provided through the cutoff date of
13 March 2021. For the BNT162b1 100 µg dose group in the younger age group, results are
only presented after Dose 1 but before Dose 2.
Full details and outputs regarding disposition, exposure, data sets, demographics, and diarycompliance for Phase 1 of Study C4591001 through the data cutoff date of 24 August 2020
(to 1 month after Dose 2) are in Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim
CSR Section 10.1.1, Section 10.3.1, Section 10.4.1, Section 10.5.1, and Section 10.6.2.1,
respectively. Full details and outputs regarding disposition through the data cutoff date of
13 March 2021 for the BNT162b2 (30 μg) group are in Module 5.3.5.1 C4591001 6-Month
Update Interim CSR Section 10.1.1.

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2.7.4.1.2.2.1. Disposition (Phase 1, Study C4591001)
Overall, 195 participants were randomized. No participants have been withdrawn due to an
AE as of the data cutoff date (24 August 2020).
In the BNT162b1 younger age group, 12 participants were randomized to each of the 3 dosegroups (10 µg, 20 µg, and 30 µg dose groups) and 9 participants to the placebo group (in the
100 µg dose group, 12 participants were randomized to vaccine and 3 participants wererandomized to placebo). In the BNT162b1 older age group, 12 participants were randomized
to each of the 3 dose groups and 9 participants were randomized to the placebo group.
In the BNT162b2 group, both the younger and older age groups, 12 participants wererandomized to each of the 3 dose groups and 9 participants were randomized to placebo.

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To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
All participants in each age group randomized to receive BNT162b2 30 μg completed thevisit at 6 months after Dose 2, with most of these 6-month visits occurring during the openlabel follow-up period. All participants in each age group randomized to the placebo group
received both doses of BNT162b2 (Dose 3 and Dose 4 in the study) during the open-label
period and completed the visit at 1 month after Dose 4, as of the data cutoff date of
13 March 2021. No participants were withdrawn from the study up to the data cutoff date.
2.7.4.1.2.2.2. Exposure (Phase 1, Study C4591001)
In the BNT162b1 younger age group, all participants randomized to the 10 µg, 20 µg, and 30µg dose groups received both doses of BNT162b1 or placebo, and all participants
randomized to the 100 µg dose group (from younger age group only) received Dose 1 of
BNT162b1 or placebo. The IRC determined not to administer the second dose of 100 µg due
to reactogenicity (these participants received BNT162b1 at 10 µg as their second dose). All
participants in the BNT162b1 older age group randomized to each dose group received bothdoses of BNT162b1 or placebo. (No participants in the older age group received BNT162b1
100 μg.) All participants in the BNT162b1 group received Dose 2 within the protocol
specified time.
In the BNT162b2 group, all participants randomized to each dose group in the younger andolder age groups received both doses of study intervention, and all participants received
Dose 2 within the protocol-specified time.
2.7.4.1.2.2.3. Safety Data Sets Analyzed (Phase 1, Study C4591001)
For BNT162b1 and BNT162b2, all participants randomized to receive study intervention in
the younger and older age groups were included in the safety population.
2.7.4.1.2.2.4. Demographic and Other Characteristics of Study Population (Phase 1,
Study C4591001)
Demographic characteristics were similar across the vaccine groups within each age groupfor participants who received BNT162b1.

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Most participants in the BNT162b1 group were White in both the younger age group andolder age group. Median age for this group was 35.0 years in the younger age group and 69.0
years in the older age group. In the BNT162b1 younger age group (up to 30 µg), 17 (37.8%)
were female and 28 (62.2%) were male (9 [60%] female and 6 [40%] male in the 100 µg
dose group); in the older age group, 32 (71.1%) were female and 13 (28.9%) were male.
Most participants in the BNT162b2 group were White in the younger age group, and allparticipants were White in the older age group. Median age in this group was 37.0 years in
the younger age group and 68.0 years in the older age group. In the BNT162b2 younger age
group, 26 (57.8%) were female and 19 (42.2%) were male; in the older age group, 28(62.2%) were female and 17 (37.8%) were male.
Baseline Medical History
The study population of the BNT162b1 and BNT162b2 groups were healthy with medical
history profiles consistent with those of the healthy general population in each age group.

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2.7.4.1.2.2.5. E-Diary Compliance (Phase 1, Study C4591001)
Transmission of e-diary data after either dose of BNT162b1 or placebo was ≥77.8% for eachday during the 7 days following any vaccination in the younger age group and older age
group, and transmission rates were similar across dose groups in both age groups.
Transmission of e-diary data after either dose of BNT162b2 or placebo was ≥75.0% for eachday during the 7 days following any vaccination in the younger and older age groups, andtransmission rates were similar across dose groups in both age groups.
2.7.4.1.2.3. Phase 2 (Study C4591001)
Results for participants in the younger (18 to 55 years) and older (56 to 85 years) age groups
in the Phase 2 portion of Study C4591001 are presented through the data cutoff date of
02 September 2020.
Full details and outputs regarding disposition, exposure, data sets, demographics, and diarycompliance for Phase 2 of Study C4591001 are in Module 5.3.5.1 C4591001 Efficacy Final
Analysis Interim CSR Section 10.1.2, Section 10.3.2, Section 10.4.2, Section 10.5.2, andSection 10.6.2.2, respectively.
2.7.4.1.2.3.1. Disposition (Phase 2, Study C4591001)
The first 360 participants enrolled as part of Phase 2 were randomized equally(180 participants each) to the BNT162b2 and placebo groups. Among participants
randomized to the BNT162b2 group, 88 participants were in the younger age group and 92
participants were in the older age group.
2.7.4.1.2.3.2. Exposure (Phase 2, Study C4591001)
Except for 1 participant in the BNT162b2 younger age group who was withdrawn after
Dose 1 but before Dose 2 and 1 participant in the placebo group (who had not yet received
Dose 2 at the time of data cutoff [02 September 2020]), all other participants received bothdoses of study intervention. The participant in the BNT162b2 younger group was withdrawn
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from the study 23 days after receiving Dose 1 (after Dose 1 but before Dose 2 because of an
SAE of gastric adenocarcinoma (Section 2.7.4.2.3.4.2). All other participants received bothdoses of vaccine. No participants received the incorrect study intervention. The majority ofparticipants received Dose 2 between 19 to 23 days after Dose 1 in the BNT162b2 (97.2%)
and placebo (96.7%) groups.
2.7.4.1.2.3.3. Safety Data Sets Analyzed (Phase 2, Study C4591001)
At the time of the data cutoff (02 September 2020), the proportions of participants in thesafety population were the same in the BNT162b2 group and the placebo group(180 participants each). Within the BNT162b2 group, 88 participants were in the younger
age group and 92 were in the older age group.

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2.7.4.1.2.3.4. Demographic and Other Characteristics of Study Population (Phase 2,
Study C4591001)
Demographic characteristics for Phase 2 were similar in the BNT162b2 group and theplacebo group for the safety population. For the BNT162b2 younger age group, 42 (47.7%)
were female and 46 (52.3%) were male. In the BNT162b2 older age group, 42 (45.7%) werefemale and 50 (54.3%) were male. Most participants were White (85.8%), followed by Blackor African American (9.2%). The proportions of Hispanic/Latino participants were similar in
the BNT162b2 and placebo groups. The median age was 56.0 years across participants ages
18 to 85 (44.0 years for the younger age group and 65.0 years for the older age group).
Baseline Medical History
The 360 participants in Phase 2 had a diverse medical history profile consistent withindividuals of the same age group in the general population. In the BNT162b2 group,
conditions in the surgical and medical procedures, immune system disorders, and metabolism
and nutrition disorders SOCs were most frequently reported.
2.7.4.1.2.3.5. E-Diary Compliance (Phase 2, Study C4591001)
Overall, transmission of e-diary data was ≥91.7% for each day during the 7 days after Dose 1of BNT162b2. After Dose 2 of BNT162b2, transmission of e-diary data was 80.6% on Day
1 and ranged from 88.9% to 91.7% for each day during Day 2 through Day 7. Transmission
rates were similar in the BNT162b2 group and the placebo group.
2.7.4.1.2.4. Phase 3 (Study C4591001)
Results for participants (≥16 years of age) in the Phase 3 portion of Study C4591001 arepresented through the data cutoff date of 13 March 2021.
Study population details and outputs (including subpopulation analyses) for Phase 3 ofStudy C4591001 are presented fully in the C4591001 6-Month Update Interim CSR:Disposition: Module 5.3.5.1 C4591001 6-Month Update Interim CSR Section 10.1.2

Protocol deviations: Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Section 10.2
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2.7.4 Summary of Clinical SafetyExposure: Module 5.3.5.1 C4591001 6-Month Update Interim CSR Section 10.3.2



Safety Data sets: Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Section 10.4.2



Demographics and Other Characteristics: Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Section 10.5.2



Diary compliance: Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Section 10.6.2.2

Note: Phase 3 tables and figures are titled as “Phase 2/3” to capture the fact that the360 Phase 2 participants are included in the overall phase 3 analyses.
2.7.4.1.2.4.1. Disposition (Phase 3, Study C4591001)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The disposition of all Phase 2/3 participants randomized is presented for the blinded placebo
controlled and open-label follow-up periods in Table 31 (Appendix D).
In this ongoing study, tables summarizing participant withdrawals may include someparticipants who were reported as withdrawn but remain in the study and are continuing to beevaluated. These participants are documented in Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Errata.
2.7.4.1.2.4.1.1. Blinded Placebo-Controlled Follow-Up Period
During the blinded placebo-controlled follow-up period, most participants randomized
received Dose 1 (99.8%) and Dose 2 (98.1%). There were 352 (1.6%) participants in the
BNT162b2 group and 528 (2.4%) participants in the placebo group who discontinued fromthe vaccination period (Dose 1 to 1 month after Dose 2) (Table 31). Most participants
completed the 1 month post-Dose 2 visit 2 (≥96.4%). Few participants in the BNT162b2 andplacebo groups were withdrawn from the study (1.6% and 2.2%, respectively), and mostwere due to withdrawals by the participant, or they were lost to follow-up.
There were 7 participants with special data issues: 8 participant identification numbers from
4 participants who enrolled into the study more than once and 3 participants whose vaccine
assignment was not confirmed in IRT at the time of data cutoff.
Three participants who were randomized and vaccinated, but actual vaccine
assignment was not confirmed in IRT at the time of data cutoff. Participants were
vaccinated as per CRF, but due to the inability to confirm consistency between thedata in the CRF and IRT, these participants were not assigned to any actual dosing
group. Safety data from these 3 participants were excluded from safety summary
tables but their safety data are listed separately (Table 34).

During the conduct of this study, 4 participants were each randomized twice withdifferent participant identification numbers at 2 different sites. Because the significant
misconduct of these participants compromised the integrity of the study data, resultsfrom these participants were excluded from all efficacy and safety analyses, including
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disposition and demographic tabulations. These participants who were discontinued
from vaccination and/or from the study are listed separately.
2.7.4.1.2.4.1.2. Open-Label Follow-Up Period
Individuals ≥16 years of age have been unblinded as they became locally eligible and wishedto know their treatment assignment to confirm prior vaccination with BNT162b2 (ifrandomized to this group), or to receive BNT162b2 (if randomized to placebo). Unblindedrecipients originally randomized to BNT162b2 continue to be followed in an open-labelmanner. Unblinded recipients originally randomized to placebo are offered BNT162b2
vaccination (Doses 3 and 4 [first and second dose of BNT162b2 30 µg, respectively]) andthereafter followed in an open-label manner.
Most participants in the BNT162b2 (96.8%) and placebo (96.4%) groups completed the
1 month post-Dose 2 visit before unblinding (Table 31).

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A total of 87 (0.4%) Phase 2/3 original BNT162b2 participants received Dose 1 of
BNT162b2 during the blinded placebo-controlled follow-up period and then received Dose 2of BNT162b2 30 µg during the open-label follow-up period (when they were unblinded).
There were 105 (0.5%) participants withdrawn from the study, and most were due towithdrawals by the participant, or they had a protocol deviation.
During the open-label follow-up period, most participants originally randomized in theplacebo group received Doses 3 and 4 (88.8% and 72.4%, respectively) of BNT162b2. There
were few participants in this group (0.1%) who were withdrawn from the study, and mostwere due to withdrawals by the participant.
The disposition of HIV-positive participants is included in this summary but summarized
separately in safety analyses.
Disposition of all participants ≥16 years of age randomized was similar by age group.
There were no clinically meaningful differences in disposition by age group, baseline
SARS-CoV-2 status, ethnicity, race, or sex.
2.7.4.1.2.4.2. Exposure (Phase 3, Study C4591001)
Almost all participants were administered study intervention as randomized; 99.7% received
Dose 1 and 98.5% received Dose 2 of BNT162b2 in the BNT162b2 group, and 99.8%
received Dose 1 and 98.0% received Dose 2 of placebo in the placebo group (Table 32 in
Appendix D).
For Dose 1, 4 participants randomized to the placebo group received BNT162b2, and2 participants randomized to the BNT162b2 group received placebo. Two participants
randomized to the BNT162b2 group and 1 participant randomized to the placebo group
received an indeterminate vaccine for Dose 1.
For Dose 2, 5 participants randomized to the placebo group received BNT162b2, and3 participants randomized to the BNT162b2 group received placebo.
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After unblinding, 88.8% of original placebo participants received Dose 3 (first dose of
BNT162b2 30 µg) and 72.4% received Dose 4 (second dose of BNT162b2 30 µg) at the timeof the data cutoff date.
The majority of participants received Dose 2 between 21 to 27 days after Dose 1 in the
BNT162b2 (62.6%) and placebo (62.7%) groups (Table 33 in Appendix D). After
unblinding, most original placebo participants received Dose 4 (second dose of BNT162b2
30 µg) between 14 to 20 (22.6%) and 21 to 27 (48.1%) days after Dose 3.
2.7.4.1.2.4.3. Safety Data Sets Analyzed (Phase 3, Study C4591001)
The safety population included a total of 44,050 participants: 22,026 participants in the
BNT162b2 group and 22,021 participants in the placebo group (Table 34 in Appendix D).
Most of the total 115 (0.3%) participants excluded from the safety population were excluded
because those participants did not receive study vaccine.

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There were no clinically meaningful differences in the safety population by age group,
baseline SARS-CoV-2 status, ethnicity, race, or sex.
During the blinded placebo-controlled follow-up period, 51.1% of participants in the
BNT162b2 group and 51.4% of participants in the placebo group had follow-up time
between ≥4 months to <6 months after Dose 2 (Table 35 in Appendix D). From Dose 2 tothe cutoff date, 54.5% of participants in the BNT162b2 group had a total follow-up time of≥6 months.
In the younger age group, 48.5% of participants in the BNT162b2 group and 48.3% ofparticipants in the placebo group had follow-up time between ≥4 months to <6 months after
Dose 2 during the blinded placebo-controlled follow up period. From Dose 2 to the cutoff
date, 51.0% of participants in the BNT162b2 group had a total follow-up time of ≥6 months.
In the older age group, 54.8% of participants in the BNT162b2 group and 55.9% ofparticipants in the placebo group had follow-up time between ≥4 months to <6 months after
Dose 2 during the blinded placebo-controlled follow-up period. From Dose 2 to the cutoff
date, 59.6% of participants in the BNT162b2 group had a total follow-up time of ≥6 months.
During the open-label follow-up period, 47.5% of original placebo participants had follow-up
time between ≥1 month to <2 months after Dose 1 of BNT162b2.
2.7.4.1.2.4.4. Demographic and Other Characteristics of Study Population (Phase 3,
Study C4591001)
2.7.4.1.2.4.4.1. Overall – Participants ≥16 Years of Age (Phase 3, Study C4591001,
Demographic and Other Characteristics of Study Population)
Demographic characteristics for all Phase 3 participants ≥16 years of age were similar in the
BNT162b2 and placebo groups (Table 4). Overall, most participants were White (82.0%),
with 9.6% Black or African American participants and 4.3% Asian participants, and all otherracial groups were ≤2.5%. There were 25.9% Hispanic/Latino participants. Median age was

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51.0 years and 50.9% of participants were male. Obesity was reported in 34.4% ofparticipants in this safety population.
Baseline SARS-CoV-2 status was positive (defined as a positive N-binding antibody result at
Visit 1, positive NAAT result at Visit 1, or medical history of COVID-19) in 3.1% ofparticipants in the BNT162b2 group and 3.3% of participants in the placebo group.

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Demographic data including participants 12 through 15 years of age enrolled in this study aresummarized in Section 2.7.4.1.2.4.4.4. Safety data for participants 12 through 15 years of age
will be reported separately.

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Table 4.

Demographic Characteristics – Phase 2/3 Subjects ≥16 Years of Age –Safety Population

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Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=22026)
nb (%)

Placebo(Na=22021)
nb (%)

Total(Na=44047)
nb (%)

Sex
Male
Female11322 (51.4)
10704 (48.6)

11098 (50.4)
10923 (49.6)22420 (50.9)
21627 (49.1)

Race
White
Black or African American
American Indian or Alaska Native
Asian
Native Hawaiian or other Pacific IslanderMultiracial
Not reported

18056 (82.0)
2098 (9.5)
221 (1.0)952 (4.3)
58 (0.3)
550 (2.5)
91 (0.4)

18064 (82.0)
2118 (9.6)
217 (1.0)942 (4.3)
32 (0.1)
533 (2.4)
115 (0.5)36120 (82.0)4216 (9.6)
438 (1.0)
1894 (4.3)
90 (0.2)
1083 (2.5)
206 (0.5)78 (0.4)

78 (0.4)

156 (0.4)

Ethnicity
Hispanic/Latino
Non-Hispanic/non-Latino
Not reported

5704 (25.9)
16211 (73.6)
111 (0.5)5695 (25.9)
16212 (73.6)
114 (0.5)11399 (25.9)
32423 (73.6)
225 (0.5)

Country
Argentina
BrazilGermanySouth Africa
TurkeyUSA2883 (13.1)
1452 (6.6)
249 (1.1)
401 (1.8)
249 (1.1)
16792 (76.2)

2881 (13.1)
1448 (6.6)
250 (1.1)
399 (1.8)
249 (1.1)
16794 (76.3)

5764 (13.1)
2900 (6.6)
499 (1.1)
800 (1.8)
498 (1.1)
33586 (76.3)

Age group (at vaccination)
16-55 Years>55 Years

13069 (59.3)
8957 (40.7)

13095 (59.5)8926 (40.5)

26164 (59.4)
17883 (40.6)

Age at vaccination (years)
Mean (SD)MedianMin, max

49.7 (15.99)
51.0(16, 89)49.6 (16.05)
51.0(16, 91)49.7 (16.02)
51.0(16, 91)

Baseline SARS-CoV-2 status
Positivec
Negatived
Missing

689 (3.1)
21185 (96.2)
152 (0.7)716 (3.3)21180 (96.2)
125 (0.6)1405 (3.2)
42365 (96.2)
277 (0.6)

Body mass index (BMI)
Underweight (<18.5 kg/m2)

271 (1.2)

304 (1.4)

575 (1.3)

Racial designation
Japanese

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Table 4.

Demographic Characteristics – Phase 2/3 Subjects ≥16 Years of Age –Safety Population
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Normal weight (≥18.5 kg/m2 - 24.9 kg/m2)
Overweight (≥25.0 kg/m2 - 29.9 kg/m2)
Obese (≥30.0 kg/m2)
Missing

BNT162b2 (30 μg)(Na=22026)
nb (%)

Placebo(Na=22021)
nb (%)

Total(Na=44047)
nb (%)

6535 (29.7)
7670 (34.8)7543 (34.2)
7 (0.0)6524 (29.6)
7558 (34.3)
7629 (34.6)
6 (0.0)13059 (29.6)
15228 (34.6)
15172 (34.4)
13 (0.0)

Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calculations.
b. n = Number of subjects with the specified characteristic.
c. Positive N-binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID-19.
d. Negative N-binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID-19.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(15:19)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adsl_s005_demo_all_p3_saf

Within each age group, most demographic characteristics were similar in the BNT162b2
group and the placebo group. Overall, 4.0% of participants in the younger age group were
SARS-CoV-2 baseline positive, and 1.9% of participants in the older age group were
SARS-CoV-2 baseline positive, and the proportions were similar in the BNT162b2 andplacebo groups. There was a lower proportion of non-Hispanic/non-Latino participants in theyounger BNT162b2 and placebo groups (68.6% and 68.8%, respectively) than in the older
BNT162b2 and placebo groups (80.9% and 80.7%, respectively).
Within each baseline SARS-CoV-2 status group, demographic characteristics were similar in
the BNT162b2 group and the placebo group. Most participants were White regardless ofbaseline status; however, there was a higher proportion of White participants with a negative
baseline status (82.9%) than with a positive baseline status (57.7%). The median age was
43.0 years in participants with a positive baseline status and 51.0 years in participants with anegative baseline status. There were 41.4% and 34.2% of participants who were obese withpositive and negative baseline status, respectively.
Baseline Medical History
Participants ≥16 years of age had a diverse medical history profile consistent with that ofindividuals in the general population in the same age group. In the BNT162b2 group,
conditions in the surgical and medical procedures (8430 [38.3%]), metabolism and nutrition
disorders (6587 [29.9%]), and immune system disorders (5987 [27.2%]; of which 3303
[15.0%] were seasonal allergy) SOCs were most frequently reported.
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Overall, 20.7% had any comorbidity (per the Charlson comorbidity index). The mostfrequently reported comorbidities were diabetes without chronic complications (7.7%),
chronic pulmonary disease (8.1%), and any malignancy (3.6%), which were reported atsimilar frequencies in each group.
In the younger age group, 13.3% of participants had any comorbidity. The most frequently
reported comorbidities were diabetes without chronic complications (3.7%) and chronic
pulmonary disease (7.4%), which were reported at similar frequencies in each vaccine group.
In the older age group, 31.6% of participants had any comorbidity. The most frequently
reported comorbidities were diabetes without chronic complications (13.6%) and chronic
pulmonary disease (9.1%), which were reported at similar frequencies in each vaccine group.

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2.7.4.1.2.4.4.1.1. Participants With Confirmed Stable HIV Disease (Phase 3, Study
C4591001, Demographic and Other Characteristics of Study Population)
Demographic characteristics for participants with confirmed stable HIV disease were similarin the BNT162b2 and the placebo groups. Overall, 54.5% of participants were Black or
African American, 40.5% of participants were White, and all other racial groups were ≤1.5%.
There were 16.0% Hispanic/Latino participants. Median age was 49.5 years and 67.5% ofparticipants were male. Obese participants made up 39.0% of this population.
2.7.4.1.2.4.4.2. Participants With At Least 6 Months Follow-Up Time – Original
BNT162b2 Participants ≥16 Years of Age (Phase 3, Study C4591001, Demographic andOther Characteristics of Study Population)
Demographic characteristics for all original BNT162b2 Phase 2/3 participants ≥16 years ofage and had at least 6 months of follow-up time after Dose 2 are presented in Table 36 inAppendix D. Overall, most participants were White (86.4%), with 7.1% Black or African
American participants and 3.8% Asian participants, and other racial groups were ≤1.6%.
There were 27.8% Hispanic/Latino participants. Median age was 53.0 years and 50.3% ofparticipants were male. Obese participants made up 34.2% of this safety population.
2.7.4.1.2.4.4.3. Original Placebo Participants ≥16 Years of Age Who Then Received
BNT162b2 (Phase 3, Study C4591001, Demographic and Other Characteristics of Study
Population)
Demographic characteristics for all original placebo Phase 2/3 participants ≥16 years of age
who then received BNT162b2 later during the open-label follow-up period are presented inTable 37 in Appendix D. Overall, most participants were White (83.1%), with 8.3% Black or
African American participants and 4.3% Asian participants, and all other racial groups were
≤2.6%. There were 25.5% Hispanic/Latino participants. Median age was 51.0 years and50.2% of participants were male. Obese participants made up 34.4% of this safety
population.

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2.7.4.1.2.4.4.4. All Participants (Phase 3, Study C4591001, Demographic and Other
Characteristics of Study Population)
Demographic characteristics for all participants (including adolescents 12 through 15 yearsof age) were similar in the BNT162b2 group and the placebo group.
2.7.4.1.2.4.5. E-Diary Compliance (Phase 3, Study C4591001)
Overall, transmission of e-diary data was ≥90.1% (range: 90.1% to 94.0%) for each day
during the 7 days after Dose 1 of BNT162b2. After Dose 2 of BNT162b2, transmission ofe-diary data was 76.5% on Day 1 and ranged from 83.8% to 85.6% for each day during
Day 2 through Day 7. Transmission rates were similar in the BNT162b2 group and theplacebo group.
2.7.4.2. Safety Results for BNT162b2

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Safety data for the primary and exploratory safety endpoints (as described in Section
2.7.4.1.1.2.1) for Phase 1, Phase 2, and Phase 3 for Study C4591001 and for Study BNT16201 are presented in the following sections:

BNT162-01: Section 2.7.4.2.1

Phase 1: Section 2.7.4.2.2

Phase 2: Section 2.7.4.2.3

Phase 3: Section 2.7.4.2.4

Safety methods are described in Section 2.7.4.1.1 with more details in Appendix B(Section 2.7.4.6.2).
Full details of safety results, including for additional endpoints, are presented as follows:
Study BNT162-01: Module 5.3.5.1 BNT162-01 CSR.
Study C4591001:


Phase 1, to 1 month after Dose 2: Module 5.3.5.1 C4591001 Efficacy Final Analysis
Interim CSR; to 6 months after Dose 2: Module 5.3.5.1 C4591001 6-Month Update
Interim CSRPhase 2, to 7 days after Dose 2: Module 5.3.5.1 C4591001 Efficacy Final Analysis
Interim CSRPhase 2/3, to 1 month after Dose 2: Module 5.3.5.1 C4591001 Efficacy Final
Analysis Interim CSR; to 6 months after Dose 2: Module 5.3.5.1 C4591001 6-Month
Update Interim CSR.

Note that data from Phase 2 participants were included in Phase 3 safety analyses.
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2.7.4.2.1. Study BNT162-01
Safety data (reactogenicity and AE analyses) are available up through the data cutoff date(23 October 2020) and are summarized below up to 1 month after Dose 2 for the younger andolder age groups. Data from the safety set are presented. This summary focuses on the 10 µg,
20 µg, and 30 µg dose levels, which correspond to the primary dose levels investigated in the
Phase 1 part of pivotal registration study, C4591001.
2.7.4.2.1.1. Reactogenicity (Phase 1, Study BNT162-01)
Reactogenicity results are up to 7 days after Dose 1 and Dose 2.
2.7.4.2.1.1.1. Local Reactions (Phase 1, Study BNT162-01)

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Overall, solicited local reactions following administration across doses of BNT162b2 were
milder and less frequent for participants compared with BNT162b1. Local reactions
generally increased in frequency and/or severity with increasing dose level and number ofdoses of BNT162b1 and BNT162b2. Most local reactions were mild or moderate in severity
and resolved within several days of onset.
For BNT162b1, the incidence of any local reactions after each dose was similar between
younger and older age groups, but local reactions were generally milder in the older group.
For BNT162b2, incidence of local reactions was generally less after each dose in the older
group compared with the younger group, and severity of reactions was similar between bothage groups.
Full details and outputs regarding local reactions for Study BNT162-01 are in Module 5.3.5.1
BNT162-01 CSR Section 12.3.
2.7.4.2.1.1.2. Systemic Events (Phase 1, Study BNT162-01)
Overall, solicited systemic events following administration across doses of BNT162b2 were
milder and less frequent for participants compared with BNT162b1. Systemic events
generally increased in frequency and/or severity with increasing dose level and number ofdoses of BNT162b1 and BNT162b2. Most systemic events were mild or moderate, arose
within the first 1 to 2 days after dosing, and were short-lived.
For BNT162b1, the incidence of any systemic events after each dose was similar between
younger and older age groups, but systemic events were generally milder in the older group.
For BNT162b2, the incidence of systemic events after each dose was similar in the older
group compared with the younger group. Reports of severe systemic events were similar
between the younger and older BNT162b2 groups and were substantially less frequent than
the severe events reported for younger and older BNT162b1 groups.
Full details and outputs regarding systemic events for Study BNT162-01 are in Module
5.3.5.1 BNT162-01 CSR Section 12.4.

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2.7.4.2.1.2. Summary of Treatment-Emergent Adverse Events (Phase 1,
Study BNT162-01)
Full details and outputs regarding the summary of adverse events for Study BNT162-01 arein Module 5.3.5.1 BNT162-01 CSR Section 12.5.1.
Overall, 40% to 45% of participants who received BNT162b1 and BNT162b2 across age
groups and across dose levels reported one or more AEs from Dose 1 through 28 days (ie,1 month) after Dose 2. There was no overall pattern between vaccine candidates with regard
to AE incidence or severity; however, AEs considered by the investigator as related to study
intervention (after omitting events captured in paper diaries for reactogenicity) were lessfrequently reported for BNT162b2 groups compared with BNT162b1.
Most AEs reported were considered by the investigator as not related to study intervention.
Most AEs were mild to moderate in severity. All AEs were reported as resolved.

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In the BNT162b1 group, 2 younger participants discontinued from the study (see Section
2.7.4.2.1.4.3) and 1 older participant experienced SAE (see Section 2.7.4.2.1.4.2). In the
BNT162b2 group, 1 younger participant discontinued from the study (see Section
2.7.4.2.1.4.3) and 1 older participant experienced an SAE (see Section 2.7.4.2.1.4.2).
No deaths occurred through the data cutoff date.
2.7.4.2.1.3. Analysis of Treatment-Emergent Adverse Events (Phase 1, Study BNT16201)
Details and outputs regarding AEs by SOC and PT, related AEs, and severe AEs forStudy BNT162-01 are in Module 5.3.5.1 BNT162-01 CSR Section 12.5.2.
2.7.4.2.1.3.1. Treatment-Emergent Adverse Events by System Organ Class andPreferred Term (Phase 1, Study BNT162-01)
From Dose 1 up to Day 28 after Dose 2 or Dose 1 (if no Dose 2), after omitting events
captured in paper diaries for reactogenicity: In the BNT162b1 younger age group, the mostfrequently reported SOCs were general disorders and administration site conditions (mostcommon PT: injection site reaction), nervous system disorders (most common PT:
headache), and respiratory, thoracic and mediastinal disorders (most common PTs: coughand oropharyngeal pain). In the BNT162b1 older age group, the most frequently reported
SOC was respiratory, thoracic and mediastinal disorders (most common PTs: cough andoropharyngeal pain); other SOCs were only reported by 1 or 2 participants each.
From Dose 1 up to Day 28 after Dose 2 or Dose 1 (if no Dose 2), after omitting events
captured in paper diaries for reactogenicity: In the BNT162b2 younger age group, the mostfrequently reported SOC was general disorders and administration site conditions (mostcommon PT: vessel puncture site pain. In the BNT162b2 older age group, the mostfrequently reported SOC was musculoskeletal and connective tissue disorders (most common
PT: back pain).

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2.7.4.2.1.3.2. Related Treatment-Emergent Adverse Events (Phase 1, Study BNT162-01)
From Dose 2 up to Day 28 after Dose 2: In the BNT162b1 younger age group, the mostfrequently reported related SOCs were general disorders and administration site conditions(most common PT: influenza like illness), nervous system disorders (most common PT:
headache), and musculoskeletal and connective tissue disorders (most common PT: myalgia).
In the BNT162b1 older age group, 1 related TEAE was reported in the 30 μg group in eachof the following SOCs: ear and labyrinth disorders, gastrointestinal disorders, and urinary
disorders.
From Dose 2 up to Day 28 after Dose 2: In the BNT162b2 younger age group, the mostfrequently reported related SOC was general disorders and administration site conditions(most common PT: injection site reaction). In the BNT162b2 older age group, 1 related
TEAE was reported in the vascular disorders SOC (PT: hot flush).
2.7.4.2.1.3.3. Severe Treatment-Emergent Adverse Events (Phase 1, Study BNT162-01)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The most frequently reported SOC with severe and related TEAEs was general disorders andadministration site conditions for the BNT162b1 younger groups. In the BNT162b1 older age
group, nervous system disorders was the most frequently reported SOC with severe TEAEs(none were sever and related).
The most frequently reported SOC with severe TEAEs was musculoskeletal and connective
tissue disorder and nervous system disorders for the BNT162b2 younger and older age
groups, respectively (no severe TEAEs were assessed as related).
2.7.4.2.1.4. Deaths, Serious Adverse Events, Safety-Related Participant Withdrawals,
and Other Significant Adverse Events (Phase 1, Study BNT162-01)
Details and outputs regarding deaths, serious adverse events, safety-related participant
withdrawals, and other significant adverse events for Study BNT162-01 are in
Module 5.3.5.1 BNT162-01 CSR Section 12.6.
2.7.4.2.1.4.1. Deaths (Phase 1, Study BNT162-01)
There were no Study BNT162-01 participants who died through the data cutoff date of
23 October 2020.
2.7.4.2.1.4.2. Treatment-Emergent Serious Adverse Events (Phase 1, Study BNT162-01)
Among BNT162b1 participants, 1 older participant in the 20 µg group had an SAE of severe
syncope (considered as not related to study intervention) after Dose 1 and study treatment
was withdrawn.
Among BNT162b2 participants, 1 older participant in 20 µg group had an SAE of ankle
fracture (considered as not related to study intervention) after receiving both doses, was listed
as recovering, and remains in follow-up.

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2.7.4.2.1.4.3. Safety-Related Participant Withdrawals (Phase 1, Study BNT162-01)
Among BNT162b1 recipients, 1 younger participant in the 10 µg group discontinued thestudy due to a moderate AE of malaise (considered as not related to study intervention) after
Dose 1 and 1 younger participant in the 60 µg group discontinued due to a dose-limiting
toxicity of pyrexia after Dose 1.
Among BNT162b2 recipients, 1 younger participant in the in the 10 µg group discontinued
the study due to a moderate AE of nasopharyngitis (considered as not related to study
intervention) after Dose 1.
2.7.4.2.1.4.4. Adverse Events of Special Interest (Phase 1, Study BNT162-01)
There were no Study BNT162-01 participants who reported any AEs of special interest
through the data cutoff date of 23 October 2020.
2.7.4.2.1.5. Clinical Laboratory Evaluations (Phase 1, Study BNT162-01)

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Full details and outputs regarding clinical laboratory evaluations for Phase 1 of Study
BNT162-01 are in Module 5.3.5.1 BNT162-01 CSR Section 12.7.
Changes from baseline in lymphocyte (low) count were reported in all dose groups after 48
hours of dosing with both BNT162b1 and BNT162b2 as a pharmacodynamics effect.
However, their values came back to normal at the subsequent visit without any clinicalconsequence and without sequelae.
Changes from baseline were small in all dose groups following the administration of both
BNT162b1 and BNT162b2. Likewise, the changes from baseline did not indicate a particulartrend in the time course of all clinical chemistry parameters, except for CRP in both
BNT162b1 and BNT162b2 younger age groups, as a pharmacodynamics effect. However,their values came back to normal at the subsequent visit without any clinical consequence. In
the older participants group, no elevated values of CRP were seen.
There were a few abnormal urinalysis parameters, but none were clinically significant except
for 1 elevated value of leukocytes (on Day 50 in younger participant in 1 μg group).
2.7.4.2.1.6. Vital Signs, Physical Findings, and Other Observations Related to Safety(Phase 1, Study BNT162-01)
Full details and outputs regarding physical examination findings for Phase 1 of Study
BNT162-01 are in Module 5.3.5.1 BNT162-01 CSR Section 12.8.
A few abnormal vital signs were reported but none of them were clinically relevant
abnormalities, except for mild or moderate elevated body temperature reported on Day 2 by 5participants in the BNT162b1 younger age group. The events were assessed as related
TEAEs, and the elevated body temperature values came back to normal at the subsequent
visit with medication.
No participants presented clinically significant ECG findings or physical examination
findings at screening or when assessed during the ongoing study.
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2.7.4.2.1.7. Conclusions (Phase 1, Study BNT162-01)
Based on Phase 1 data from the FIH Study BNT162-01, BNT162b2 was safe and welltolerated in healthy adults 18 to 85 years of age, with no unanticipated safety findings.
Reactogenicity and AEs tended to increase in incidence and/or severity with increasing doseof BNT162b2. Reactogenicity was mostly mild to moderate and short-lived after dosing, and
the AE profile and clinical laboratory results did not suggest any safety concerns.
2.7.4.2.2. Phase 1 (Study C4591001)

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Safety data are available up through the data cutoff dates noted below and are summarized atvarious time points relative to Dose 1 or Dose 2 as follows:

Safety results for Phase 1 vaccine candidates BNT162b1 and BNT162b2 for both
adult age groups are presented up to 1 month after Dose 2 (or 24 August 2020 data
cutoff date) at the 10 µg, 20 µg, and 30 µg dose levels.



Safety results for BNT162b1 at the 100 µg dose level in the younger age group arepresented up to 3 weeks after Dose 1 or to before Dose 2 based on the data cutoff dateof 24 August 2020. Note that the group of participants 18 to 55 years of age who
received 100 µg BNT162b1 did not receive a second dose of 100 µg BNT162b2 per
IRC decision, and instead, they were given 10 µg for Dose 2. At the time of the data
cutoff date, 11 of 12 participants in this group received Dose 2 of BNT162b1 at 10 µg
but results for Dose 2 are not yet available at the time of this report.

Long-term follow-up from 1 month after Dose 2 to approximately 6 months after
Dose 2 (as of unblinding date) of AEs and SAEs for Phase 1 participants who
received BNT162b2 30 µg are also presented (these data are based on the 13
March 2021 data cutoff date). Note: Adverse event data for the BNT162b2 30 µggroup, from Dose 1 to the unblinding date, are summarized in Module 5.3.5.1
C4591001 6-Month Update CSR Section 12.1.2 and Section 12.1.3.

All doses tested for BNT162b1 and BNT162b2 (10 µg, 20 µg, and 30 µg) were safe and welltolerated except for BNT162b1 at 100 µg, which was discontinued after the first dose due tothe reactogenicity profile. BNT162b2 at 30 µg was selected to proceed into the Phase 2/3
portion of the study because this dose and construct provided the optimum combination of afavorable reactogenicity profile and a robust immune response.
2.7.4.2.2.1. Reactogenicity (Phase 1, Study C4591001)
Reactogenicity results are up to 7 days after Dose 1 and Dose 2.
2.7.4.2.2.1.1. Local Reactions (Phase 1, Study C4591001)
Overall, for both the BNT162b1 and the BNT162b2 recipients, and in both age groups, painat the injection site was the most frequent local reaction. Redness and swelling occurred lessfrequently in the BNT162b2 group and in the BNT162b1 group. In both the BNT162b1 and
BNT162b2 groups, the frequency of local reactions was lower in the older age group

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2.7.4 Summary of Clinical Safetycompared to the younger age group, and there was a trend of a higher frequency of local
reactions with increased dose. Local reactions were short-lived.
Full details and outputs regarding local reactions for Phase 1 of Study C4591001 are in
Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.1.1.
2.7.4.2.2.1.2. Systemic Events (Phase 1, Study C4591001)

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Overall, within 7 days after Dose 1, fatigue was generally the most frequently reported
systemic event in the both the younger and older BNT162b1 groups and in the older
BNT162b2 group; while headache and fatigue were most frequently reported in the younger
BNT162b2 dose group. Overall, within 7 days after Dose 2, headache was the mostfrequently reported systemic event in the both the younger and older BNT162b1 groups andfatigue was the most frequently reported systemic event in the both the younger and older
BNT162b2 groups. Chills was generally reported at a higher frequency after Dose 2 and at ahigher frequency in the BNT162b1 group than in the BNT162b2 group. Fever was reported
more frequently in the younger BNT162b1 group after Dose 2 than in the older BNT162b2
group. For both the BNT162b1 and the BNT162b2 recipients, after the first and second doseand in both age groups, the majority of systemic events were mild or moderate in severity (noGrade 4 systemic events) and generally short-lived.
Full details and outputs regarding systemic events for Phase 1 of Study C4591001 are in
Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.1.2.
2.7.4.2.2.2. Summary of Adverse Events (Phase 1, Study C4591001)
Full details and outputs regarding the summary of adverse events for Phase 1 of Study
C4591001 (including for participants in the BNT162b1 100 µg dose group) are in Module
5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.1.3.1 (24 August 2020
data cutoff date).
All AEs from Dose 1 through the data cutoff date of 24 August 2020 were included in thesummary for all dose levels for each vaccine candidate and age group other than
BNT162b1 100 µg group for which AEs from Dose 1 to before Dose 2 were summarized.
Additionally, long-term follow-up (from 1 month to approximately 4 months after Dose 2 [asof 14 November 2020 cutoff date]) of AEs for Phase 1 participants who received
BNT162b2 30 µg were summarized.
Overall, fewer participants reported at least 1 AE after Dose 1 in the older BNT162b2 group(8.3% to 25.0%) compared to the younger (41.7% to 50.0%) and older (25.0% to 58.3%)
BNT162b1 groups and the younger BNT162b2 group (33.3% to 41.7%).
No SAEs, AEs leading to withdrawals, or deaths were reported in either age group for either
the BNT162b1 or BNT162b2 groups up to 1 month after Dose 2.
To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
For the BNT162b2 30 µg group, during the additional follow-up to the unblinding date(approximately 6 months of follow-up after Dose 2), no additional AEs were reported in the
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younger or older age group except for 1 severe SAE (neuritis due to an antecubital fossa
blood draw) reported in the younger age group (Section 2.7.4.2.2.3.1).
2.7.4.2.2.3. Analysis of Adverse Events (Phase 1, Study C4591001)
Details and outputs regarding AEs by SOC and PT, related AEs, immediate AEs, and severe
AEs for Phase 1 of Study C4591001 (including for participants in the BNT162b1 100 µg
dose group) are in Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section
12.1.3.2.
2.7.4.2.2.3.1. Adverse Events by System Organ Class and Preferred Term (Phase 1,
Study C4591001)

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AE by SOC and PT summaries included AEs from Dose 1 to 1 month after Dose 2 for allgroups other than BNT162b1 100-ug group for which AEs from Dose 1 to 3 weeks after
Dose 1 or from Dose 1 to before Dose 2 were summarized.
General disorders and administration site conditions was the most commonly reported SOC
in the older BNT162b1 group and the younger BNT162b2 group. The most commonly
reported SOC was gastrointestinal disorders in the younger BNT162b1 group and nervous
system disorders in the older BNT162b2 group. Generally, most PTs were reported by≤2 participants per dose group.
To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
For the BNT162b2 30 µg group, during the additional follow-up to the unblinding date(approximately 6 months of follow-up after Dose 2), an additional severe SAE (neuritis) was
reported by 1 participant in the younger age group; per the participant’s medical examinationand history, this event was linked to a blood draw, and the investigator considered there wasa reasonable possibility that the event neuritis was related to clinical trial procedure(antecubital fossa blood draw) but unrelated to vaccination.
2.7.4.2.2.3.2. Related Adverse Events (Phase 1, Study C4591001)
Overall, general disorders and administration site conditions was the most commonly
reported SOC for the younger and older BNT162b1 groups and the younger BNT162b2
group. In the older BNT162b2 group, nausea, reported in 1 (8.3%) participant, was the only
related AE.
To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
Additional follow-up through the unblinding date (approximately 6 months of follow-up after
Dose 2) did not identify any additional participants with related AEs in the BNT162b2 30 µggroup.

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2.7.4.2.2.3.3. Immediate Adverse Events (Phase 1, Study C4591001)
In the BNT162b1 group, no participants in the younger group reported an immediate AE
after Dose 1 at the 30 µg dose level, and there were no participants in either age group who
reported any immediate AEs after Dose 2 of BNT162b1.
In the BNT162b2 group, 3 participants in the younger age group reported an immediate AE
after Dose 1 (including 1 report of injection site pain from a participant in the 30 µg dosegroup). After Dose 2 of BNT162b2, 1 participant in the 20 µg dose group reported an
immediate AE. There were no participants in the older age group who reported any
immediate AE after any dose of BNT162b2.
2.7.4.2.2.3.4. Severe Adverse Events (Phase 1, Study C4591001)

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In the BNT162b1 group, 2 severe AEs were reported in the younger age group (pyrexia[102.4°F] 2 days after Dose 2 [30 µg dose group] and sleep disorder 1 day after Dose 1 [100µg dose group]; both were determined by the investigator to be related to study intervention)and 2 severe AEs were reported in the older age group (herpes zoster 2 days after Dose 1 [20µg dose group], which was considered unrelated, and fatigue 1 day after Dose 2 [30 µg dosegroup], which was considered related).
In the BNT162b2 younger age group, 1 participant with a history of migraines reported asevere migraine 7 days after Dose 1 (30 µg dose group, considered unrelated). In the
BNT162b2 older age group, 2 participants reported a severe AE: muscle spasms 2 days after
Dose 2 (30 µg dose group, considered unrelated to BNT162b2) and radiculopathy 3 days
after Dose 1 (placebo), considered unrelated to study intervention.
To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
Additional follow-up through the unblinding date (approximately 6 months of follow-up after
Dose 2) for the BNT162b2 30 µg group identified an additional severe SAE (neuritis due toan antecubital fossa blood draw), reported in the younger age group (Section 2.7.4.2.2.3.1).
2.7.4.2.2.4. Deaths, Serious Adverse Events, Safety-Related Participant Withdrawals,
and Other Significant Adverse Events (Phase 1, Study C4591001)
Details and outputs regarding deaths, serious adverse events, safety-related participant
withdrawals, and other significant adverse events for Phase 1 of Study C4591001 are in
Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.1.4.
2.7.4.2.2.4.1. Deaths (Phase 1, Study C4591001)
There were no Phase 1 participants who died through the 24 August 2020 data cutoff date
and through the unblinding date.
2.7.4.2.2.4.2. Serious Adverse Events (Phase 1, Study C4591001)
There were no Phase 1 participants who reported any SAEs from Dose 1 through the data
cutoff date of 24 August 2020.

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To the Data Cutoff Date of 13 March 2021 for BNT162b2 (30 μg)
Additional follow-up through the unblinding date (approximately 6 months of follow-up after
Dose 2) for the BNT162b2 30 µg group identified an additional severe SAE (neuritis due toan antecubital fossa blood draw), reported in the younger age group (Section 2.7.4.2.2.3.1).
2.7.4.2.2.4.3. Safety-Related Participant Withdrawals (Phase 1, Study C4591001)
There were no Phase 1 participants with any AEs leading to withdrawal from the study
through the 24 August 2020 data cutoff date and through the unblinding date.
2.7.4.2.2.4.4. Other Significant Adverse Events (Phase 1, Study C4591001)
AEs of special interest were not defined for Phase 1 of this study.
2.7.4.2.2.4.5. Other Safety Assessments (Phase 1, Study C4591001)
2.7.4.2.2.4.5.1. Pregnancy – Phase 1
Pregnancy was not reported in any Phase 1 participants through the 24 August 2020 data
cutoff date and through the unblinding date.
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2.7.4.2.2.5. Clinical Laboratory Evaluations (Phase 1, Study C4591001)
Details and outputs regarding clinical laboratory evaluations for Phase 1 of Study C4591001
are in Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.1.5.
Overall, 1 to 3 days after Dose 1, there were transient decreases in lymphocytes(<0.8 × LLN), which returned to normal by 6 to 8 days after Dose 1, in the younger and older
BNT162b1 and BNT162b2 groups. Most shifts were from normal or Grade 1 to Grade 1, 2,
or 3 decrease in lymphocyte counts, which returned to normal by 6 to 8 days after Dose 1 andwere observed in all age and dose groups. The incidence of decreased lymphocyte counts
was lower for BNT162b2 recipients compared with BNT162b1 recipients. Shifts fromnormal to Grade 1 (younger BNT162b1 group) or Grade 2 (older BNT162b2 group)
neutrophil decrease were also observed but were infrequent.
Overall, clinical chemistry and other hematology abnormalities were observed infrequently.
None of the laboratory abnormalities were associated with clinical findings.
2.7.4.2.2.6. Physical Examination Findings (Phase 1, Study C4591001)
Overall, there were fewer abnormalities noted during physical examinations after BNT162b2
than after BNT162b1 in both age groups. Full details and outputs regarding physicalexamination findings for Phase 1 of Study C4591001 are in Module 5.3.5.1 C4591001
Efficacy Final Analysis Interim CSR Section 12.1.6.
2.7.4.2.2.7. Narratives (Phase 1, Study C4591001)
Narratives generated for Phase 1 are provided in Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Section 14.

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2.7.4.2.2.8. Conclusions (Phase 1, Study C4591001)
Based on Phase 1 data from Study C4591001, BNT162b2 was safe and well-tolerated inyounger healthy adults 18 to 55 years of age, and in older healthy adults 65 to 85 years ofage, with no unanticipated safety findings. Reactogenicity and AEs were generally milder
and less frequent in participants in the older group compared with the younger group andoverall tended to increase with increasing BNT162b2 dose. Reactogenicity was mostly mild
to moderate and short-lived after dosing, and the AE profile did not suggest any safetyconcerns. Clinical laboratory evaluations showed a transient decrease in lymphocytes thatwas observed in all age and dose groups after Dose 1, which resolved within approximately
1 week, was not associated with any other clinical sequelae, and was not consideredclinically relevant.
2.7.4.2.3. Phase 2 (Study C4591001)
Reactogenicity, AE, and SAE data for the 360 participants in the Phase 2 portion of the study
are presented up to the data cutoff date of 02 September 2020. Adverse event results beyond
7 days after Dose 2, as defined in the protocol objectives, are included in Phase 3 analyses(see Section 2.7.4.2.4).

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2.7.4.2.3.1. Reactogenicity (Phase 2, Study C4591001)
Reactogenicity results are up to 7 days after Dose 1 and Dose 2.
2.7.4.2.3.1.1. Local Reactions (Phase 2, Study C4591001)
Details and outputs regarding local reactions for Phase 2 of Study C4591001 are in Module
5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.2.1.
Frequency and Severity of Local Reactions
After the first and second dose of BNT162b2 and in both age groups, the majority of local
reactions were mild or moderate in severity, and no Grade 4 (potentially life-threatening)
local reactions were reported. In the BNT162b2 group, pain at the injection site was reported
more frequently in the younger age group (N=88 post-dose 1; N=86 post-dose 2) than in theolder age group (N=92 post-dose 1; N=91 post-dose 2), and frequency was similar after
Dose 1 compared with Dose 2 of BNT162b2 in the younger age group (85.2% vs. 80.2%,
respectively) and in the older age group (70.7% vs. 72.5%, respectively). In the placebogroup, pain at the injection site was reported at similar frequencies (7.8% to 10.2%) in theyounger and older age groups after Dose 1 and Dose 2.
In the BNT162b2 group, redness and swelling were similar in the younger and older age
group after Dose 1. After Dose 2, the frequency of redness and swelling was slightly higher
in the older age group (7.7% and 12.1%, respectively) than in the younger age group (3.5%
and 3.5%, respectively). In the placebo group, only 1 participant in the older age groupreported redness after Dose 1, and no swelling was reported.
One participant in the BNT162b2 group (older age group) reported severe injection site pain
after Dose 1, and 1 participant in the younger age group reported severe injection site pain
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after Dose 2. One participant in the BNT162b2 group (older age group) reported severe
redness after Dose 2.
Overall, across age groups, pain at the injection site was the most frequent local reaction anddid not increase after Dose 2, and redness and swelling were generally similar in frequency
after Dose 1 and Dose 2.
Onset and Duration
Across age groups, local reactions for the BNT162b2 group after either dose had a median
onset day between Day 1.0 and Day 3.0 (Day 1.0 was the day of vaccination), and ranges
were generally similar in the younger and older age groups. Across age groups, after either
dose of BNT162b2, local reactions resolved after a median duration of 1.0 to 3.0 days, which
was generally similar in the younger and older age groups.
2.7.4.2.3.1.2. Systemic Events (Phase 2, Study C4591001)
Details and outputs regarding systemic events for Phase 2 of Study C4591001 are in Module
5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.2.2.

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Frequency and Severity of Systemic Events
In the BNT162b2 group, systemic events were generally reported more frequently and wereof higher severity in the younger group (N=88 post-dose 1; N=86 post-dose 2) comparedwith the older group (N=92 post-dose 1; N=91 post-dose 2), with frequencies and severity
increasing with number of doses (Dose 1 vs Dose 2). Vomiting and diarrhea were exceptions
with vomiting infrequent and similar in both age groups and vomiting and diarrhea similar
after each dose. Frequencies of systemic events in the younger and older BNT162b2 groups(Dose 1 vs Dose 2) are listed below:


Fatigue: younger group (50.0% vs 59.3%) compared to older group (35.9% vs 52.7%)

Headache: younger group (31.8% vs 51.2%) compared to older group (27.2% vs36.3%)



Muscle pain: younger group (23.9% vs 45.3%) compared to older group (14.1% vs28.6%)



Chills: younger group (9.1% vs 40.7%) compared to older group (7.6% vs 20.9%)



Joint pain: younger group (9.1% vs 17.4%) compared to older group (4.3% vs 16.5%)Fever: younger group (3.4% vs 17.4%) compared to older group (0.0% vs 11.0%).

Vomiting: similar in both age groups and after either dose.



Diarrhea: reported less frequently in the older group and was similar after each dose.

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Systemic events were generally reported less frequently in the placebo group than in the
BNT162b2 group, for both age groups and doses, with some exceptions. In the younger age
group, fever, headache, chills, vomiting, and diarrhea after Dose 1, and vomiting after Dose 2were reported at similar frequencies in both the placebo and BNT162b2 groups. In the older
age group, vomiting, diarrhea, muscle pain, and joint pain after Dose 1, and vomiting anddiarrhea after Dose 2 were reported at similar frequencies in the placebo and BNT162b2
groups.
Use of antipyretic/pain medication was slightly less frequent in the older age group after bothdoses but increased in both age groups overall after Dose 2 as compared with after Dose 1.
Use of antipyretic/pain medication was less frequent in the placebo group than in the
BNT162b2 group.
After the first and second dose and in both age groups, the majority of systemic events weremild or moderate in severity, and no Grade 4 (potentially life-threatening) systemic eventswere reported. Across age groups, severe systemic events were only reported after Dose 2 of
BNT162b2 overall and included fever (1.1%), fatigue (4.0%), headache (2.8%),
chills (2.3%), and muscle pain (1.7%).

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Onset and Duration
Across age groups, systemic events after both doses of BNT162b2 had a median onset day
between Day 2.0 to Day 3.0 (Day 1.0 was the day of vaccination), and ranges were similar in
the younger and older age groups. Across age groups, systemic events for this group after
either dose resolved with a median duration of 1 day, which was similar in the younger andolder age groups. The median duration of fever and chills after either dose for both age
groups was 1 day. There was no clear difference in the durations of systemic events that
occurred after Dose 1 compared to those that occurred after Dose 2.
2.7.4.2.3.2. Summary of Adverse Events (Phase 2, Study C4591001)
Full details and outputs regarding the summary of adverse events for Phase 2 of Study
C4591001 are in Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section
12.2.3.1.
AE reporting for 360 participants evaluated in Phase 2 as of the data cutoff date
(14 November 2020) includes at least 2 months of follow-up. The number of participants
who reported at least 1 AE from Dose 1 to 7 days after Dose 2 was similar in the BNT162b2
group compared with the placebo group, which was generally similar in the 2 vaccine groups
in the younger and older age groups. (9.1% vs 11.1% and 4.3% vs 8.9%, respectively). Twosevere events were reported for 2 participants in the BNT162b2 younger age group: myalgia(AE) and gastric adenocarcinoma (SAE) (Section 2.7.4.2.3.3.4 and Section 2.7.4.2.3.4.2,
respectively). The SAE of gastric adenocarcinoma occurred 23 days after receiving Dose 1.
Both events were assessed by the investigator as not related to study intervention.

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2.7.4.2.3.3. Analysis of Adverse Events (Phase 2, Study C4591001)
Full details and outputs regarding AEs by SOC and PT, related AEs, immediate AEs, andsevere AEs for Phase 2 of Study C4591001 are in Module 5.3.5.1 C4591001 Efficacy Final
Analysis Interim CSR Section 12.2.3.2.
2.7.4.2.3.3.1. Adverse Events by System Organ Class and Preferred Term (Phase 2,
Study C4591001)
The number of participants who reported at least 1 AE was similar in the BNT162b2 groupcompared to the placebo group from Dose 1 to 7 days after Dose 2.

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In the younger age group, 8 (9.1%) and 10 (11.1%) participants reported at least 1 AE in the
BNT162b2 group and the placebo group, respectively. In the older age group, 4 (4.3%) and 8(8.9%) participants reported at least 1 AE in the BNT162b2 group and the placebo group,
respectively.
Overall, most AEs reported up to 7 days after Dose 2 were in the SOCs of gastrointestinal
disorders (3 [1.7%] in the BNT162b2 group and 2 [1.1%] in the placebo group), generaldisorders and administration site conditions (3 [1.7%] in the BNT162b2 group and7 [3.9%] in the placebo group), and musculoskeletal and connective tissue disorders(3 [1.7%] in the BNT162b2 group and 1 [0.6%] in the placebo group).
The most frequently reported AE by PT was injection site pain (3 [3.4%]) in the younger
BNT162b2 group, which all occurred on the day of vaccination with Dose 1 during thereporting period for local reactions. Two events resolved within 3 days, and 1 event resolved
11 days later. All other AEs by PT were reported in ≤2 participants in each vaccine group.
One participant in the older BNT162b2 group had an AE of contusion in the upper left arm
deltoid region, which was assessed by the investigator as related to study intervention.
2.7.4.2.3.3.2. Related Adverse Events (Phase 2, Study C4591001)
The number of participants with AEs assessed by the investigator as related to study
intervention from Dose 1 to 7 days after Dose 2 were low in frequency and similar in the
BNT162b2 group and placebo group. Within the BNT162b2 group, a similar proportion ofparticipants in the young and old age groups reported related AEs. Most investigatorassessed related AEs were reactogenicity events in the SOC of general disorders andadministration site conditions, and they were reported by a similar proportion of participantsin the BNT162b2 group overall compared with the placebo group, with injection site pain
being the PT reported most frequently and exclusively in the BNT162b2 younger age group.
2.7.4.2.3.3.3. Immediate Adverse Events (Phase 2, Study C4591001)
There were no immediate AEs after any dose of BNT162b2 30 µg or placebo.
2.7.4.2.3.3.4. Severe or Life-Threatening Adverse Events (Phase 2, Study C4591001)
Two participants (both in the BNT162b2 younger age group) reported severe events ofmyalgia (AE) and gastric adenocarcinoma (SAE, discussed in Section 2.7.4.2.3.4.2). The
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participant who reported myalgia had scapular muscle pain, which began 2 days after Dose 2
and which lasted 12 days. Both events were assessed by the investigator as not related to
study intervention.
2.7.4.2.3.4. Deaths, Serious Adverse Events, Safety-Related Participant Withdrawals,
and Other Significant Adverse Events (Phase 2, Study C4591001)
Full details and outputs regarding deaths, serious adverse events, safety-related participant
withdrawals, and other significant adverse events for Phase 2 of Study C4591001 are in
Module 5.3.5.1 C4591001 Efficacy Final Analysis Interim CSR Section 12.2.4.
2.7.4.2.3.4.1. Deaths (Phase 2, Study C4591001)
There were no Phase 2 participants who died through the data cutoff date of
02 September 2020.
2.7.4.2.3.4.2. Serious Adverse Events (Phase 2, Study C4591001)

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From Dose 1 to 7 days after Dose 2, 1 participant (BNT162b2 younger age group) had an
SAE of gastric adenocarcinoma 23 days after Dose 1, which was assessed by the investigator
as not related to study intervention. The SAE was ongoing at the time of the data cutoff, andthe participant was withdrawn from the study because of the SAE.
2.7.4.2.3.4.3. Safety-Related Participant Withdrawals (Phase 2, Study C4591001)
The participant in the BNT162b2 younger age group who reported an SAE of gastricadenocarcinoma (Section 2.7.4.2.3.4.2) was discontinued from the study on Day 23 after
Dose 1 of BNT162b2.
2.7.4.2.3.4.4. Other Significant Adverse Events (Phase 2, Study C4591001)
AEs of special interest were not defined for Phase 2 of this study; however, targeted medical
events were monitored throughout the study (see Section 2.7.4.2.4.3.4).
2.7.4.2.3.5. Narratives (Phase 2, Study C4591001)
Narratives for the Phase 2 participants who were withdrawn from the study because of an
SAE through the data cutoff date (14 November 2020) are provided in Module 5.3.5.1
C4591001 Efficacy Final Analysis Interim CSR Section 14.
2.7.4.2.3.6. Conclusions (Phase 2, Study C4591001)
Based on Phase 2 data from 360 participants in Study C4591001, BNT162b2 at 30 µg wassafe and well-tolerated in adults 18 to 85 years of age. Reactogenicity and AEs weregenerally milder and less frequent in participants in the older group (≥56 years of age)compared with the younger group (≤55 years of age). Reactogenicity was mostly mild tomoderate and short-lived after dosing, and the AE profile did not suggest any serious safetyconcerns. No treatment-related SAEs were reported, and incidence of discontinuations due to
AEs up to the data cutoff date (representing at least 2 months of follow-up after Dose 2) was
low. There were no deaths as of the data cutoff date (02 September 2020). Phase 2 safety

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data were concordant with safety data in the Phase 1 portion of the study, both overall andwith regard to younger and older participants.
2.7.4.2.4. Phase 3 (Study C4591001)
Safety data are available up to the data cutoff date of 13 March 2021. Reactogenicity data arefrom the 9839 participants in the reactogenicity subset (Section 2.7.4.2.4.1). Adverse Event
data are provided for ~44,000 participants as described in Section 2.7.4.2.4.2.
2.7.4.2.4.1. Reactogenicity (Phase 3, Study C4591001)
The reactogenicity data were collected by participants’ e-diary for reporting prompted local
reactions and systemic events for 7 days after each dose.
Reactogenicity results are up to 7 days after Dose 1 and Dose 2.
2.7.4.2.4.1.1. Local Reactions (Phase 3, Study C4591001)
Details and outputs regarding local reactions for Phase 3 of Study C4591001 are in Module
5.3.5.1 C4591001 6-Month Update CSR Section 12.2.1.

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Frequency and Severity of Local Reactions
In the BNT162b2 group, pain at the injection site was reported more frequently in theyounger age group (N=2899 post-Dose 1; N=2682 post-Dose 2) than in the older age group(N=2008 post-Dose 1; N=1860 post-Dose 2), and frequency was similar after Dose 1
compared with Dose 2 of BNT162b2 in the younger age group (83.7% vs 78.3%) and in theolder group (70.1% vs 66.1%) (Figure 1 and Figure 2, respectively). In the placebo group,
pain at the injection site after Doses 1 and 2 was reported at slightly higher frequencies in theyounger age group (14.2% and 11.6%, respectively) than in the older age group (9.3% and7.8%, respectively).
In the BNT162b2 group, frequencies of redness and swelling were similar in the younger andolder age group after Doses 1 and 2. Frequencies of redness were similar after Dose 1
compared with Dose 2 of BNT162b2 in the younger age group (5.4% vs 5.6%) and in theolder age group (5.3% vs 7.2%). Frequencies of swelling were similar after Dose 1 comparedwith Dose 2 of BNT162b2 in the younger age group (6.3% vs 6.8%, respectively) and in theolder age group (7.0% vs 7.8%). In the placebo group, redness and swelling were reported
infrequently in the younger (≤1.0%) and older (≤1.2%) groups after Doses 1 and 2.
Overall, across age groups, pain at the injection site did not increase after Dose 2, andredness and swelling were generally similar in frequency after Dose 1 and Dose 2. Severe
redness and swelling were reported infrequently and were similar between the younger andolder age groups (≤0.7%) after any dose. Severe pain at the injection site occurred more
frequently in the younger age group compared to the older age group (2.5% vs 0.7%). Afterthe first and second dose and in both age groups, the majority of local reactions were mild or
moderate in severity, and no Grade 4 local reactions were reported.

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Subgroup Analyses
There were 177 BNT162b2 and 187 placebo participants with baseline positive
SARS-CoV-2 status, and 4701 BNT162b2 and 4690 placebo participants with baseline
negative SARS-CoV-2 status, respectively. For local reactions the frequency of redness,swelling, and pain at the injection site after any dose of BNT162b2 was 8.5%, 10.2%, and80.2% compared with 9.9%, 11.1%, and 84.5% for those positive and negative at baseline,
respectively. While the frequency of local reactions was numerically higher in those negative
at baseline, these differences are not clinically meaningful.
Onset and Duration

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The median onset for local reactions after either dose of BNT162b2 was between Day 1.0
and Day 2.0 (Day 1.0 was the day of vaccination) in the younger age group and between
Day 1.0 and Day 3.0 in the older age group. Local reactions resolved with median durations
between 1.0 and 2.0 days in both age groups.

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Figure 1. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days After Each Dose, by Age Group(Reactogenicity Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: 16 Through 55 Years of Age – Safety Population

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Figure 2. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days After Each Dose, by Age Group(Reactogenicity Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: >55 Years of Age

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2.7.4.2.4.1.1.1. Participants with Confirmed Stable HIV Disease (Phase 3, Study
C4591001, Local Reactions)

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Local reactions in participants with confirmed stable HIV disease were similar to thoseobserved for all participants ≥16 years of age by severity (Figure 3), onset day, and median
duration. The frequency of pain at the injection site was similar after Dose 1 compared with
Dose 2 of BNT162b2 (63.0% vs 53.3%). The frequency of redness and swelling was similar
after Dose 1 compared with Dose 2 of BNT162b2 (redness: 3.7% vs 6.7%; swelling: 5.6% vs
8.3%, respectively). There was 1 (1.7%) severe reaction (pain at the injection site) reported
after Dose 2 of BNT162b2 and no Grade 4 reactions were reported.

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Figure 3. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days After Each Dose (Reactogenicity
Subset) – Blinded Placebo-Controlled Follow-up Period – Phase 2/3 HIV-Positive Subjects ≥16 Years of Age –Safety Population

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2.7.4.2.4.1.2. Systemic Events (Phase 3, Study C4591001)
Details and outputs regarding systemic events for Phase 3 of Study C4591001 are in Module
5.3.5.1 C4591001 6-Month Update CSR Section 12.2.2.
Frequency and Severity of Local Reactions
Systemic events were generally increased in frequency and severity in the younger group(Figure 4) compared with the older group (Figure 5), with frequencies and severity increasing
with number of doses (Dose 1 vs Dose 2). Vomiting and diarrhea were exceptions, whichwere reported similarly infrequently in both age groups and at similar incidences after eachdose.

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Systemic events in the younger group compared with the older group, with frequencies
increasing with number of doses (Dose 1 vs Dose 2), were:

fatigue: younger group (49.4% vs 61.5%) compared to older group (33.7% vs 51.0%)

headache: younger group (43.5% vs 54.0%) compared to older group (25.0% vs 39.4%)

muscle pain: younger group (22.9% vs 39.3%) compared to older group (13.6% vs28.9%)

chills: younger group (16.5% vs 37.8%) compared to older group (6.5% vs 23.4%)

joint pain: younger group (11.8% vs 23.8%) compared to older group (8.7% vs 19.0%)

fever: younger group (4.1% vs 16.4%) compared to older group (1.3% vs 11.8%)

vomiting: younger group (1.2% vs 2.2%) compared to the older group (0.5% vs 0.7%)diarrhea: younger group (10.7% vs 10.0%) compared to the older group (8.4% vs 8.2%).

Systemic events were generally reported less frequently in the placebo group than in the
BNT162b2 group, for both age groups and doses, with some exceptions. In the younger age
group, vomiting and diarrhea (after Dose 1 and Dose 2) were reported at similar frequencies
in the placebo group and the BNT162b2 group (Figure 4). In the older age group, vomiting
and diarrhea (after Dose 1 and Dose 2) were reported at similar frequencies in the placebogroup and the BNT162b2 group (Figure 5).
Following both Dose 1 and Dose 2, use of antipyretic/pain medication was slightly lessfrequent in the older age group (19.0% vs 37.0%) than in the younger age group (27.8% vs45.2%) after both doses, and medication use increased in both age groups after Dose 2 ascompared with after Dose 1. Use of antipyretic/pain medication was less frequent in theplacebo group than in the BNT162b2 group and was similar after Dose 1 and Dose 2 in theyounger and older placebo groups (ranging from 9.3% to 13.7%).

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Severe fever (>38.9°C to 40.0°C) increased in frequency with the number of doses (Dose 1
versus Dose 2) in younger (0.3% vs 1.5%) and older (0.0% vs 0.4%) participants who
received BNT162b2 and was reported in 0.1% of participants who received placebo in bothage groups after both doses. One participant in the younger BNT162b2 group reported feverof 41.2°C only on Day 2 after Dose 2 and was nonfebrile for all other days of the reporting
period. Grade 4 fever was not reported in the older BNT162b2 group or in any placebo
participants.
After the first and second dose and in both age groups, the majority of systemic events weremild or moderate in severity.

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Subgroup Analyses
There were 177 BNT162b2 and 187 placebo participants with baseline positive
SARS-CoV-2 status, and 4701 BNT162b2 and 4690 placebo participants with baseline
negative SARS-CoV-2 status. For any fever after either dose there were 31 (17.5%)
compared to 714 (15.1%) in those positive and negative for SARS-CoV-2 at baseline,
respectively. Severe fever (>38.9°C to 40.0°C) was reported in 1 (0.6%) participant and 49(1.0%) participants in those positive and negative for SARS-CoV-2 at baseline, respectively.
The frequency for other systemic events after any dose was numerically lower for thosepositive at baseline: fatigue, headache and chills the frequency was 54.2%, 49.7% and 32.8%
compared with 65%, 57.4%, 34.7% for those positive and negative for SARS-CoV-2 atbaseline, respectively. Joint pain was another exception where 27.1% compared to 25.0%
were reported between those positive and negative for SARS-CoV-2 at baseline. Note thatthe baseline SARS-CoV-2 positive subgroup included far fewer participants the negative
subgroup, so their results should be interpreted with caution.
Onset and Duration
Systemic events in the younger and older age groups after either dose of BNT162b2 had a
median onset day between Day 2.0 and Day 4.0 (Day 1.0 was the day of vaccination) and
resolved with a median duration of 1 day in both age groups.

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Figure 4. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose, by Age Group(Reactogenicity Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: 16 Through 55 Years

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Figure 5. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose, Age Group(Reactogenicity Subset) – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Age Group: >55 Years

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2.7.4.2.4.1.2.1. Participants with Confirmed Stable HIV Disease (Phase 3, Study
C4591001, Systemic Events)

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Systemic events from participants with confirmed stable HIV disease were similar to thoseobserved for all participants ≥16 years of age by severity (Figure 6), onset day, and duration.
Fever, headache, chills, and joint pain increased in frequency from Dose 1 to Dose 2 while
fatigue, vomiting, diarrhea, and muscle pain were similar after each dose. There were nosevere systemic events after Dose 1 of BNT162b2 but after Dose 2, there was 1 (1.7%)
severe fever (>38.9°C to 40.0°C), 3 (5.0%) participants with severe fatigue, 2 (3.3%)
participants with severe headache, 1 (1.7%) participant with severe chills, and 1 (1.7%)
participant with severe diarrhea. There were no grade 4 systemic events reported after either
dose.

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Figure 6. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose (Reactogenicity
Subset) – Blinded Placebo-Controlled Follow-up Period – Phase 2/3 HIV-Positive Subjects ≥16 Years of Age –Safety Population

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2.7.4.2.4.2. Adverse Events (Phase 3, Study C4591001)

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AE safety data are from either the blinded placebo-controlled follow-up period, the openlabel observational follow-up period, or both. The time periods and safety analysis groups arepresented below and in Figure 7.
Blinded placebo-controlled follow-up period from Dose 1 to 1 month after Dose 2(frequencies) (Section 2.7.4.2.4.2.1)

Blinded placebo-controlled follow-up period from Dose 1 to the unblinding date (IRs)(Section 2.7.4.2.4.2.2)

Open-label follow-up period – original BNT162b2 participants (IRs)(Section 2.7.4.2.4.2.3)

Blinded placebo-controlled and open-label follow-up periods from Dose 1 to 6
months after Dose 2 – original BNT162b2 participants (frequencies)(Section 2.7.4.2.4.2.4)

Open-label follow-up period – original placebo participants who then received
BNT162b2 (IRs) (Section 2.7.4.2.4.2.5)

For AE analyses beyond 1 month after Dose 2, and for AEs after unblinding, incidence rates(IRs) per 100 Person-Years are reported (as opposed to frequencies) to account for thevariable exposure since unblinding began for individual participants.
In this ongoing study, tables summarizing participant withdrawals may include someparticipants who were reported as withdrawn but remain in the study and are continuing to beevaluated. These participants are documented in Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Errata.

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Figure 7

Study C4591001 Phase 3 Safety Analyses: Time Periods and Analysis
GroupsFull details and outputs regarding adverse events for Phase 3 of Study C4591001 are in
Module 5.3.5.1 C4591001 6-Month Update CSR Section 12.2.3.
2.7.4.2.4.2.1. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to 1 Month
After Dose 2 (Phase 3, Study C4591001)
2.7.4.2.4.2.1.1. Summary of Adverse Events: Blinded Placebo-Controlled Follow-Up
Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study C4591001)
An overview of AEs from Dose 1 to 1 month after Dose 2 for the 43,847 participants during
the blinded placebo-controlled follow-up period (including those analyzed in Phase 2) ispresented in Table 5. The numbers of overall participants who reported at least 1 AE and at
least 1 related AE were higher in the BNT162b2 group (30.2% and 23.9%, respectively) as
compared with the placebo group (13.9% and 6.0%, respectively). The higher frequencies in
the BNT162b2 group was due to terms consistent with reactogenicity reported at greater
frequency in the BNT162b2 group vs the placebo group. This pattern is further described in
Section 2.7.4.2.4.2.1.2.1. Severe AEs were reported by 1.2% and 0.7% in in the BNT162b2
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and placebo groups respectively, and life-threatening AEs were similar (0.1% in bothgroups).
SAEs and AEs leading to withdrawal were reported by ≤0.6% and ≤0.2%, respectively, inboth groups. Discontinuations due to related AEs were reported in 13 participants in the
BNT162b2 group and 11 participants in the placebo group (0.1% in both groups).
From Dose 1 to 1 month after Dose 2, there were 3 deaths in the BNT162b2 group and 5
deaths in the placebo group during the blinded follow-up period (Section 2.7.4.2.4.3.1).

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In the younger age group, the number of participants who reported at least 1 AE from Dose 1
to 1 month after Dose 2 was 4233 (32.6%) and 1871 (14.4%) in the BNT162b2 and placebogroups, respectively. In the older age group, the number of participants who reported at least
1 AE from Dose 1 to 1 month after Dose 2 was 2384 (26.7%) and 1177 (13.2%) in the
BNT162b2 and placebo groups, respectively.

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Table 5.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2 – Blinded Placebo-Controlled Follow-up Period– Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Adverse Event

BNT162b2 (30 μg)(Na=21926)
nb (%)

Placebo(Na=21921)
nb (%)

6617 (30.2)
5241 (23.9)
262 (1.2)
21 (0.1)
127 (0.6)
3 (0.0)71 (0.3)
21 (0.1)
32 (0.1)
13 (0.1)
10 (0.0)
3 (0.0)3 (0.0)3048 (13.9)
1311 (6.0)
150 (0.7)
26 (0.1)
116 (0.5)
066 (0.3)
26 (0.1)
36 (0.2)
11 (0.1)
10 (0.0)
7 (0.0)5 (0.0)Any event
Relatedc
SevereLife-threatening
Any serious adverse event
Relatedc
SevereLife-threatening
Any adverse event leading to withdrawal
Relatedc
SevereLife-threatening
Deatha. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number ofsubjects reporting at least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:09)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s091_all_pd2_p3_saf1

2.7.4.2.4.2.1.1.1. Participants with Confirmed Stable HIV Disease: Blinded PlaceboControlled Follow-Up Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study
C4591001, Summary of Adverse Events)
From Dose 1 to 1 month after Dose 2, the subset of 200 HIV-positive participants during theblinded placebo-controlled follow-up period showed generally similar trends as the overall
population (likewise attributed to reactogenicity reported in the BNT162b2 group). The
numbers of HIV-positive participants who reported at least 1 AE and at least 1 related AE
were higher in the BNT162b2 group (26.0% and 19.0%, respectively) as compared with theplacebo group (13.0% and 3.0%, respectively). In this group, there was 1 severe AE and 1
AE leading to withdrawal (both were in the BNT162b2 group), and there were no SAEs ordeaths.

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2.7.4.2.4.2.1.2. Analysis of Adverse Events: Blinded Placebo-Controlled Follow-Up
Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study C4591001)
2.7.4.2.4.2.1.2.1. Adverse Events by System Organ Class and Preferred Term: Blinded
Placebo-Controlled Follow-Up Period From Dose 1 to 1 Month After Dose 2 (Phase 3,
Study C4591001)
There are no Tier 1 AEs identified for this program.
Tier 2 AEs (defined as an event rate ≥1.0% in any vaccine group [PT level]) reported from
Dose 1 to 1 month after Dose 2 are presented in Figure 8.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Most Tier 2 AEs were reactogenicity events and all were reported in 4 SOCs: generaldisorders and administration site conditions, musculoskeletal and connective tissue disorders,
nervous system disorders, and gastrointestinal disorders. The proportions of participants
reporting Tier 2 AEs were generally higher in the BNT162b2 group (N=21,926; ranging from
1.1% to 13.3%) than in the placebo group (N=21,921; ranging from 0.3% to 1.9%). Most of
the PTs were in the SOC of general disorders and administration site conditions:






injection site pain (2915 [13.3%] BNT162b2 vs 397 [1.8%] placebo)
pyrexia (1517 [6.9%] BNT162b2 vs 77 [0.4%] placebo)
fatigue (1463 [6.7%] BNT162b2 vs 379 [1.7%] placebo)
chills (1365 [6.2%] BNT162b2 vs 120 [0.5%] placebo)
pain (628 [2.9%] BNT162b2 vs 61 [0.3%] placebo).

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Figure 8. Forest Plot of Tier 2 Adverse Events Reported From Dose 1 to 1 Month After Dose 2 – Blinded PlaceboControlled Follow-up Period – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

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From Dose 1 to 1 month after Dose 2 during the blinded placebo-controlled follow-up
period, 6617 (30.2%) BNT162b2 participants and 3048 (13.9%) placebo participants
reported at least 1 AE. Most reported AEs were in SOCs with reactogenicity events.
(Table 6).


general disorders and administration site conditions (4725 [21.5%] BNT162b2 vs
993 [4.5%] placebo)
musculoskeletal and connective tissue disorders (1804 [8.2%] BNT162b2 vs 527[2.4%] placebo)
nervous system disorders (1565 [7.1%] BNT162b2 vs 600 [2.7%] placebo)
gastrointestinal disorders (699 [3.2%] BNT162b2 vs 464 [2.1%] placebo).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The number of BNT162b2 participants who reported at least 1 AE from Dose 1 to 1 monthafter Dose 2 was 4233 (32.6%) and 2384 (26.7%) in the younger and older groups,
respectively. In the younger versus older BNT162b2 age groups, AE frequencies in above
SOCs were:general disorders and administration site conditions (3161 [24.3%] vs 1564 [17.5%])
musculoskeletal and connective tissue disorders (1201 [9.2%] vs 603 [6.8%])
nervous system disorders (1067 [8.2%] vs 498 [5.6%])
gastrointestinal disorders (440 [3.4%] vs 259 [2.9%])

As shown in Table 6, the most frequently reported AEs in the BNT162b2 group by PT
overall were injection site pain (2915 [13.3%]), pyrexia (1517 [6.9%]), fatigue (1463[6.7%]), chills (1365 [6.2%]), headache (1339 [6.1%]), and myalgia (1239 [5.7%]). During
this time period from Dose 1 to 1 month after Dose 2, most of these AEs were reported
during the e-diary 7-day reporting period.
The frequency of AEs in the SOC of investigations was higher in the BNT162b2 group(0.8%) as compared with the placebo group (0.2%) mainly due to the higher frequency of the
PT Body Temperature increased (120 in the BNT162b2 group and 12 in the placebo group).
In the skin and subcutaneous tissue disorders SOC, there were 17 participants who reportednight sweats in the BNT162b2 group (compared to 3 in the placebo group), and all but 1 ofthese participants reported the AE within the first 7 days after Dose 1 or 2, respectively, andthere were 31 participants who reported hyperhidrosis in the BNT162b2 group (compared to
9 in the placebo group), and all but 3 of these participants reported the AE within the first 7
days after Dose 1 or 2.
Nineteen study participants reported events in the Hepatobiliary Disorders SOC(14 BNT162b2 recipients and 5 placebo recipients) (Table 6). Of the 19 total participants,
3 participants had hepatic events:One participant in the placebo group reported hepatic cirrhosisOne participant in the placebo group reported nonalcoholic fatty liver disease

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One participant in the BNT162b2 group reported alcoholic cirrhosis

The remaining 16 participants reported biliary events (cholecystitis/cholecystitis acute,biliary colic, bile duct stone, and biliary dyskinesia): 13 participants in the BNT162b2 groupand 3 participants in the placebo group.
In the BNT162b2 group, 8 participants reported cholelithiasis (1 reported an event eachof cholelithiasis and cholecystitis), 1 participant reported cholecystitis acute,
2 participants reported biliary colic, and 1 participant each reported bile duct stone/biliary
dyskinesia.

In the placebo group, there were 3 participants who reported the following: 1 participant
reported an event each of cholecystitis acute and cholelithiasis, 1 participant reportedcholecystitis acute, and 1 participant reported cholelithiasis.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

In the nervous systems disorder SOC, there were 3 participants who reported facial paralysis
in the BNT162b2 group (compared to none in the placebo group). More details are presented
in Section 2.7.4.2.4.3.4.1.2.
For lymphadenopathy the frequency in the BNT162b2 group was 0.4% compared to thefrequency of 0.0% on the placebo group. Most AEs of lymphadenopathy in the BNT162b2
group were judged by the investigator as related to study intervention (further discussed in
Section 2.7.4.2.4.3.4.1.3.
Other events of clinical interest that were identified by the sponsor are discussed in
Section 2.7.4.2.4.3.4.
Post Hoc Analysis
Beyond the 9839 participants in the Phase 2/3 reactogenicity subset, events related toreactogenicity are no longer reported using an e-diary but are instead reported as AEs. As
previously described in the final analysis interim CSR dated 03 December 2020, an analysis
was conducted to evaluate if the imbalance in AEs observed from Dose 1 to 1 month after
Dose 2 was attributed to reactogenicity events. The analysis examined the AEs reported
within 7 days after each dose, which represented the reactogenicity reporting period. The
time period was chosen because many AEs were reported in the SOCs of general disorders
and administration site conditions, musculoskeletal and connective tissue disorders, andnervous system disorders, which includes AEs consistent with reactogenicity events, andcould only be attributed to reactogenicity if they occurred during this time period as opposed
to occurring up to 1 month from each dose.
PTs reported from Dose 1 to 7 days after Dose 1 and from Dose 2 to 7 days after Dose 2 in
the SOCs of general disorders and administration site conditions (injection site pain, chills,
fatigue, and pyrexia), musculoskeletal and connective tissue disorders (myalgia), and nervous
system disorders (headache) represented the majority of PTs reported in those SOCs. AEs
reported from Dose 1 to 7 days after Dose 1 and from Dose 2 to 7 days after Dose 2 werelargely attributable to reactogenicity events. This observation provides a reasonable
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explanation for the greater rates of AEs observed overall in the BNT162b2 group comparedwith the placebo group, consistent with results previously described in the final analysis
interim CSR dated 03 December 2020.
In addition to analysis of AEs corresponding to e-diary terms that were reported within
7 days after Dose 1 or Dose 2 that are attributable to reactogenicity, additional consideration
was given to AE terms that are reported at higher frequency in the BNT162b2 groupcompared to placebo. The following additional AEs were identified: pain in extremity,
decreased appetite, lethargy, asthenia, malaise, night sweats, and hyperhidrosis. Careful
examination of these terms after either dose of BNT162b2 shows that these events are
clustered within the 7-day period when reactogenicity events are known to occur. Since themajority of the participants did not have an e-diary and reported reactogenicity as AEs, there
is considerable leeway in how symptoms are described by participants from multiple
countries, interpreted by investigators and reported as AEs. As these events are occurring
when reactogenicity is being reported, these events are considered to be attributable to theexperience of reactogenicity events and are plausibly associated with local reactions andsystemic events.

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These PTs were reported more frequently in the younger age group.

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

Placebo(Na=21921)
nb (%)(95% CIc)

Any event6617 (30.2)(29.6, 30.8)3048 (13.9)(13.4, 14.4)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymphadenopathy
Iron deficiency anaemia
Anaemia
Lymph node pain
Blood loss anaemia
Leukocytosis
Neutropenia
Thrombocytopenia
Thrombocytosis
Hypochromic anaemia
Leukopenia
Lymphadenitis
Lymphadenopathy mediastinal
Lymphopenia
Splenomegaly

105 (0.5)
83 (0.4)
8 (0.0)4 (0.0)7 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)0(0.4, 0.6)
(0.3, 0.5)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

19 (0.1)
7 (0.0)1 (0.0)4 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)00000
1 (0.0)(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Palpitations
Tachycardia
Atrial fibrillation
Coronary artery disease
Acute myocardial infarction
Acute coronary syndrome
Cardiac failure congestive
Myocardial infarction
Angina unstable
Bradycardia
Left ventricular hypertrophy
Mitral valve incompetenceAngina pectoris
Aortic valve incompetence
Arrhythmia
Arteriospasm coronary
Atrial flutter

56 (0.3)
6 (0.0)13 (0.1)
7 (0.0)3 (0.0)3 (0.0)1 (0.0)2 (0.0)01 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)0(0.2, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

50 (0.2)
14 (0.1)
6 (0.0)9 (0.0)3 (0.0)2 (0.0)3 (0.0)2 (0.0)4 (0.0)2 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)(0.2, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

2 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)000
1 (0.0)001 (0.0)01 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)000
1 (0.0)01 (0.0)001 (0.0)001 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Congenital bladder neck obstruction
Congenital cystic kidney disease
Heart disease congenital
Type V hyperlipidaemia

2 (0.0)01 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)1 (0.0)001 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
VertigoEar painTinnitus
Vertigo positional

65 (0.3)
25 (0.1)
11 (0.1)
9 (0.0)8 (0.0)(0.2, 0.4)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

43 (0.2)
20 (0.1)
6 (0.0)8 (0.0)3 (0.0)(0.1, 0.3)
(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Cardiac arrest
Mitral valve prolapse
Myocardial ischaemia
Sinus tachycardia
Supraventricular tachycardia
Tricuspid valve incompetence
Ventricular extrasystoles
Acute left ventricular failure
Arrhythmia supraventricularAtrioventricular block complete
Atrioventricular block first degree
Bundle branch block left
Bundle branch block right
Cardiac disorder
Cardiac failure acute
Cardiovascular disorder
Coronary artery dissection
Coronary artery occlusion
Junctional ectopic tachycardia
Left atrial enlargement
Left ventricular dysfunction
Myocarditis
Pericardial effusion
Pericarditis
Tachyarrhythmia
Ventricular arrhythmia
Ventricular tachycardia

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

3 (0.0)3 (0.0)1 (0.0)01 (0.0)001 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)00
1 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)001 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

ENDOCRINE DISORDERS
Hypothyroidism
Hypogonadism
Thyroid mass
Autoimmune thyroiditis
GoitreHyperprolactinaemia
Thyroid cyst

13 (0.1)
6 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)0(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

5 (0.0)4 (0.0)00000
1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EYE DISORDERS
Cataract
Eye pain
Eye irritation
Vision blurred
Chalazion
Vitreous detachment
Blepharitis
Conjunctival haemorrhage
Conjunctivitis allergic
Dry eye
Keratitis
Ocular hyperaemia
Glaucoma

60 (0.3)
6 (0.0)7 (0.0)6 (0.0)7 (0.0)3 (0.0)4 (0.0)2 (0.0)1 (0.0)3 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

50 (0.2)
5 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)2 (0.0)3 (0.0)1 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)(0.2, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Deafness unilateral
Ear discomfort
Cerumen impaction
Ear disorder
Meniere's disease
Allergic otitis media
Deafness
Deafness neurosensory
Ear pruritus
Eustachian tube dysfunction
Hyperacusis
Hypoacusis
Otorrhoea
Sudden hearing loss
Tympanic membrane perforation

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Lacrimation increased
Photophobia
Retinal detachment
Vitreous floaters
Asthenopia
Blepharospasm
Diplopia
Eye pruritus
Amaurosis fugax
Choroidal neovascularisation
Conjunctival hyperaemia
Conjunctival oedema
Corneal irritation
Dacryostenosis acquired
Diabetic retinopathy
Episcleritis
Eye allergy
Eye inflammation
Eye swelling
Eyelid haematoma
Eyelid oedema
Eyelid pain
Eyelids pruritus
IritisOcular discomfort
Retinal artery occlusion
Scleral discolouration
Swelling of eyelid
Ulcerative keratitis
Visual acuity reduced
Visual impairment

2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)02 (0.0)1 (0.0)01 (0.0)001 (0.0)001 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)0000
1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GASTROINTESTINAL DISORDERS
Diarrhoea
NauseaVomiting
Toothache
Abdominal pain upper699 (3.2)
248 (1.1)
274 (1.2)
66 (0.3)
24 (0.1)
25 (0.1)(3.0, 3.4)
(1.0, 1.3)
(1.1, 1.4)
(0.2, 0.4)
(0.1, 0.2)
(0.1, 0.2)464 (2.1)
188 (0.9)87 (0.4)
32 (0.1)
27 (0.1)
15 (0.1)(1.9, 2.3)
(0.7, 1.0)
(0.3, 0.5)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

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2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Abdominal pain
Gastrooesophageal reflux disease
Dyspepsia
Odynophagia
Constipation
Dental caries
Gastritis
Haemorrhoids
Aphthous ulcer
Abdominal discomfort
Abdominal distension
Flatulence
Irritable bowel syndrome
Dry mouth
Large intestine polyp
Abdominal pain lower
Dysphagia
Inguinal hernia
Stomatitis
Diverticulum
Gastrointestinal disorder
Hiatus hernia
Paraesthesia oral
Retching
Small intestinal obstruction
Cheilitis
Faeces soft
Food poisoning
Gingival pain
Hypoaesthesia oral
Lip swelling
Rectal haemorrhage
Swollen tongue
Tooth impacted
Umbilical hernia
Colitis microscopic
Diverticulum intestinal

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

19 (0.1)
12 (0.1)
12 (0.1)
13 (0.1)
7 (0.0)8 (0.0)3 (0.0)3 (0.0)8 (0.0)5 (0.0)6 (0.0)4 (0.0)4 (0.0)2 (0.0)2 (0.0)2 (0.0)3 (0.0)1 (0.0)2 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)3 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)0

19 (0.1)
16 (0.1)
11 (0.1)
8 (0.0)11 (0.1)
6 (0.0)10 (0.0)
10 (0.0)
3 (0.0)5 (0.0)1 (0.0)3 (0.0)3 (0.0)4 (0.0)4 (0.0)3 (0.0)2 (0.0)4 (0.0)3 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)02 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)2 (0.0)02 (0.0)(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Eructation
Gingival discomfort
Glossodynia
Haematochezia
Mouth ulceration
Noninfective gingivitis
Oral pain
Pancreatitis
Pancreatitis acute
Parotid duct obstruction
Salivary gland calculus
Abdominal adhesions
Abdominal hernia
Abdominal rigidity
Abnormal faeces
Acute abdomen
Anal pruritus
Angular cheilitis
Appendix disorder
Chronic gastritis
ColitisColitis ulcerative
Diverticular perforation
Diverticulum intestinal haemorrhagic
Epiploic appendagitis
Femoral hernia
Frequent bowel movements
Gastric polyps
Gastric ulcer
Gastric ulcer haemorrhage
Gastritis erosive
Gastrointestinal haemorrhage
Gastrointestinal mucosa hyperaemia
Gastrointestinal pain
Gastrointestinal sounds abnormal
Gingival bleeding
Gingival swelling

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)2 (0.0)2 (0.0)02 (0.0)2 (0.0)1 (0.0)01 (0.0)01 (0.0)01 (0.0)000
1 (0.0)001 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)000

1 (0.0)1 (0.0)002 (0.0)001 (0.0)2 (0.0)1 (0.0)2 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)000
1 (0.0)1 (0.0)0000
1 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Glossitis
Haemorrhoidal haemorrhage
Hypoaesthesia teeth
Impaired gastric emptying
Incarcerated inguinal hernia
Intestinal obstruction
Lip oedema
Loose tooth
Obstructive pancreatitis
Oesophageal food impaction
Oesophageal spasm
Oesophageal ulcer
Oesophageal varices haemorrhage
Oesophagitis
Oral discomfort
Oral lichenoid reaction
Oral mucosa haematoma
Palatal disorder
Pancreatic failure
Peptic ulcer
Proctalgia
Salivary gland mucocoele
Teething
Tongue discolouration
Tongue discomfort
Tongue oedema
Tongue pruritus
Tongue ulceration
Tooth disorder
Varices oesophageal
Volvulus
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONSInjection site pain
FatiguePyrexia
Chills

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)01 (0.0)1 (0.0)001 (0.0)1 (0.0)000
1 (0.0)1 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

0
0
0
0
0
1 (0.0)01 (0.0)01 (0.0)001 (0.0)1 (0.0)001 (0.0)1 (0.0)1 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)4725 (21.5)(21.0, 22.1)

993 (4.5)(4.3, 4.8)2915 (13.3)
1463 (6.7)
1517 (6.9)
1365 (6.2)(12.8, 13.8)(6.3, 7.0)
(6.6, 7.3)
(5.9, 6.6)

397 (1.8)379 (1.7)
77 (0.4)
120 (0.5)(1.6, 2.0)
(1.6, 1.9)
(0.3, 0.4)
(0.5, 0.7)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Pain
Injection site erythema
Injection site swelling
MalaiseAsthenia
Injection site pruritus
Injection site bruising
Influenza like illness
Chest pain
Injection site warmth
Axillary pain
Injection site induration
Injection site oedema
Non-cardiac chest pain
Oedema peripheral
Peripheral swelling
Chest discomfort
Feeling hot
Injection site discomfort
Swelling face
Injection site haematoma
Injection site haemorrhage
Injection site reaction
Injection site mass
Injection site paraesthesia
Swelling
Adverse drug reaction
Cyst
Feeling abnormal
Injection site discolouration
Injection site nodule
Injection site papule
Injection site rash
Sensation of foreign body
Application site pain
Face oedema
Feeling cold

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

628 (2.9)185 (0.8)140 (0.6)130 (0.6)
76 (0.3)
38 (0.2)
13 (0.1)
23 (0.1)
12 (0.1)
14 (0.1)
14 (0.1)
10 (0.0)
12 (0.1)
5 (0.0)5 (0.0)5 (0.0)5 (0.0)8 (0.0)6 (0.0)2 (0.0)2 (0.0)3 (0.0)5 (0.0)3 (0.0)2 (0.0)2 (0.0)3 (0.0)2 (0.0)3 (0.0)2 (0.0)3 (0.0)3 (0.0)2 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)61 (0.3)
28 (0.1)
23 (0.1)
22 (0.1)
25 (0.1)
5 (0.0)18 (0.1)
4 (0.0)11 (0.1)
5 (0.0)3 (0.0)4 (0.0)0
6 (0.0)5 (0.0)5 (0.0)4 (0.0)1 (0.0)3 (0.0)5 (0.0)4 (0.0)3 (0.0)1 (0.0)1 (0.0)2 (0.0)2 (0.0)01 (0.0)01 (0.0)001 (0.0)0000(2.6, 3.1)
(0.7, 1.0)
(0.5, 0.8)
(0.5, 0.7)
(0.3, 0.4)
(0.1, 0.2)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.2, 0.4)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Injury associated with device
Medical device pain
NoduleSluggishness
ThirstVessel puncture site bruise
Vessel puncture site haematoma
Application site erythema
Application site pruritus
Application site rash
Application site reaction
Capsular contracture associated with breast implant
Death
Discomfort
Drug withdrawal syndrome
Effusion
Exercise tolerance decreased
Facial pain
Gait disturbanceIllness
Induration
Inflammation
Injection site dermatitis
Injection site hyperaesthesia
Injection site injury
Injection site irritation
Injection site lymphadenopathy
Injection site macule
Injection site plaqueInjection site urticaria
Mass
Medical device site granuloma
Mucosal disorderShoulder injury related to vaccine administration
Temperature intolerance
Therapeutic response unexpected
Vaccination site induration

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)02 (0.0)01 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)000
1 (0.0)1 (0.0)01 (0.0)2 (0.0)02 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)01 (0.0)1 (0.0)001 (0.0)001 (0.0)00000
1 (0.0)000
1 (0.0)01 (0.0)1 (0.0)1 (0.0)001 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Vaccination site pain
Vaccination site swelling
Vascular stent occlusion
Vessel puncture site induration00
1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

HEPATOBILIARY DISORDERS
Cholelithiasis
Cholecystitis acute
Biliary colic
Bile duct stone
Biliary dyskinesia
Cholecystitis
Cirrhosis alcoholic
Hepatic cirrhosis
Nonalcoholic fatty liver disease

14 (0.1)
8 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)00(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

5 (0.0)2 (0.0)2 (0.0)00000
1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Seasonal allergy
Drug hypersensitivity
Food allergy
Hypersensitivity
Allergy to arthropod bite
Allergy to arthropod sting
Anaphylactic reaction
Anaphylactic shock
Milk allergy

22 (0.1)
8 (0.0)7 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)00(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

25 (0.1)
13 (0.1)
5 (0.0)3 (0.0)3 (0.0)000
1 (0.0)1 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INFECTIONS AND INFESTATIONSUrinary tract infection
Tooth infection
Sinusitis
Cellulitis
Herpes zoster
Ear infection
Conjunctivitis
Hordeolum
Cystitis
Gastroenteritis
Rhinitis
Tooth abscess

337 (1.5)
58 (0.3)
24 (0.1)
18 (0.1)
12 (0.1)
12 (0.1)
9 (0.0)9 (0.0)8 (0.0)6 (0.0)5 (0.0)5 (0.0)9 (0.0)(1.4, 1.7)
(0.2, 0.3)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

365 (1.7)
52 (0.2)
29 (0.1)
27 (0.1)
15 (0.1)
10 (0.0)
12 (0.1)
11 (0.1)
11 (0.1)
11 (0.1)
10 (0.0)
10 (0.0)
6 (0.0)(1.5, 1.8)
(0.2, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Upper respiratory tract infection
Diverticulitis
Otitis externa
Otitis media
Vulvovaginal mycotic infection
Appendicitis
Gingivitis
Oral herpes
Acute sinusitis
Pneumonia
Skin infection
Vaginal infection
Vulvovaginal candidiasis
Fungal skin infection
Onychomycosis
Periodontitis
Pharyngitis streptococcal
Pyelonephritis
Folliculitis
Furuncle
Localised infection
Nasopharyngitis
Otitis media acute
Paronychia
Tonsillitis
Genital herpes
Herpes simplex
Influenza
Pharyngitis
Postoperative wound infection
Tinea versicolour
Bacterial vulvovaginitis
Bronchitis
Chronic sinusitis
Eye infection
Gingival abscess
Impetigo

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

9 (0.0)8 (0.0)6 (0.0)7 (0.0)5 (0.0)7 (0.0)5 (0.0)4 (0.0)1 (0.0)2 (0.0)3 (0.0)04 (0.0)1 (0.0)3 (0.0)3 (0.0)4 (0.0)5 (0.0)5 (0.0)3 (0.0)2 (0.0)3 (0.0)3 (0.0)3 (0.0)002 (0.0)3 (0.0)1 (0.0)2 (0.0)2 (0.0)3 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)6 (0.0)5 (0.0)7 (0.0)6 (0.0)8 (0.0)3 (0.0)5 (0.0)5 (0.0)7 (0.0)5 (0.0)4 (0.0)7 (0.0)3 (0.0)5 (0.0)3 (0.0)3 (0.0)2 (0.0)1 (0.0)02 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)5 (0.0)4 (0.0)2 (0.0)1 (0.0)3 (0.0)2 (0.0)2 (0.0)02 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Infected bite
Parotitis
PustuleSubcutaneous abscessTinea infection
Abscess
Abscess limb
Acarodermatitis
Anal abscess
Appendicitis perforated
Bacterial vaginosis
COVID-19
Conjunctivitis bacterial
Erysipelas
Escherichia urinary tract infection
Gastroenteritis viral
Kidney infection
Labyrinthitis
Laryngitis
Ophthalmic herpes zoster
Oral candidiasis
Papilloma viral infection
Peritonsillar abscessPharyngotonsillitis
Rash pustular
Sialoadenitis
Sinusitis bacterial
Trichomoniasis
Vulvovaginitis
Abdominal abscess
Abscess intestinal
Abscess jaw
Abscess neckAnal fistula infection
Bacterial blepharitis
Bacterial infection
Bacterial sepsis

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

2 (0.0)1 (0.0)3 (0.0)1 (0.0)01 (0.0)002 (0.0)1 (0.0)000
2 (0.0)1 (0.0)1 (0.0)1 (0.0)02 (0.0)1 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)01 (0.0)01 (0.0)1 (0.0)2 (0.0)02 (0.0)3 (0.0)1 (0.0)2 (0.0)2 (0.0)01 (0.0)2 (0.0)2 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)2 (0.0)01 (0.0)001 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Balanitis candida
Bartholin's abscess
Bartholinitis
Blister infected
Bone abscessBrain abscessCampylobacter infection
Carbuncle
Cellulitis orbital
Clostridium difficile infection
Complicated appendicitis
Coxsackie viral infection
Dental fistula
Dermatitis infected
Device related infection
Empyema
Eye infection bacterial
Genital herpes simplex
Gonorrhoea
Groin abscessHelicobacter gastritis
Helicobacter infection
Hepatitis A
Hepatitis C
Injection site abscess
Lyme disease
Meningitis bacterial
Nail infection
Oral fungal infection
Oral infection
Orchitis
Osteomyelitis
Otitis media bacterial
Parasitic gastroenteritis
Pelvic inflammatory disease
Peritoneal abscess
Peritonitis

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)001 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)00000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)000
000
1 (0.0)
0
0
0
0
0
0
0
0
1 (0.0)01 (0.0)01 (0.0)1 (0.0)000
1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Pharyngitis bacterial
Pilonidal cyst
Pulmonary tuberculosis
Puncture site infection
Pyelonephritis acuteRespiratory tract infection viral
Sepsis
Shigella sepsis
Skin bacterial infection
Soft tissue infection
Staphylococcal infection
Subacute endocarditis
Suspected COVID-19
Syphilis
Tinea cruris
Tonsillitis bacterial
Urosepsis
Varicella
Viral infection
Viral upper respiratory tract infection
Wound infection0
1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)001 (0.0)01 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)001 (0.0)0000
1 (0.0)001 (0.0)01 (0.0)1 (0.0)01 (0.0)001 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INJURY, POISONING AND PROCEDURALCOMPLICATIONS
Fall
Ligament sprain
Skin laceration
Contusion
Exposure during pregnancy
Muscle strain
Road traffic accident
Skin abrasion
Arthropod bite
Limb injury
Foot fracture
Joint injury
Tooth fracture
Procedural pain

215 (1.0)(0.9, 1.1)

269 (1.2)(1.1, 1.4)

48 (0.2)
19 (0.1)
14 (0.1)
12 (0.1)
10 (0.0)
14 (0.1)
9 (0.0)8 (0.0)12 (0.1)
7 (0.0)5 (0.0)5 (0.0)7 (0.0)8 (0.0)(0.2, 0.3)
(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

51 (0.2)
22 (0.1)
22 (0.1)
19 (0.1)
19 (0.1)
15 (0.1)
15 (0.1)
13 (0.1)
7 (0.0)11 (0.1)
8 (0.0)8 (0.0)6 (0.0)3 (0.0)(0.2, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.1)
(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

CONFIDENTIAL
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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Meniscus injury
Animal bite
Arthropod sting
Facial bones fracture
Joint dislocation
Rib fracture
Ankle fracture
Concussion
Muscle rupture
Wound
Chest injury
Corneal abrasion
Ligament rupture
Thermal burn
Vaccination complication
Epicondylitis
Fibula fracture
Hand fracture
Head injury
Humerus fracture
Overdose
Radius fracture
Tendon rupture
Wrist fracture
Bone contusion
Craniocerebral injury
Maternal exposure during pregnancy
Muscle injury
Spinal compression fracture
Ulna fracture
Administration related reaction
Burns second degree
Cervical vertebral fracture
Ligament injury
Lower limb fracture
Procedural dizziness
Skin injury

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

4 (0.0)2 (0.0)3 (0.0)4 (0.0)7 (0.0)3 (0.0)2 (0.0)3 (0.0)1 (0.0)2 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)5 (0.0)1 (0.0)2 (0.0)3 (0.0)2 (0.0)03 (0.0)2 (0.0)01 (0.0)1 (0.0)02 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)000
1 (0.0)6 (0.0)6 (0.0)5 (0.0)4 (0.0)1 (0.0)5 (0.0)4 (0.0)3 (0.0)5 (0.0)4 (0.0)2 (0.0)2 (0.0)3 (0.0)3 (0.0)03 (0.0)2 (0.0)1 (0.0)2 (0.0)4 (0.0)1 (0.0)2 (0.0)4 (0.0)3 (0.0)2 (0.0)3 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)000
2 (0.0)2 (0.0)2 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred TermStress fracture
Tendon injury
Upper limb fracture
Alcohol poisoning
Anaemia postoperative
Brain contusion
Burn oral cavity
Burns first degree
Clavicle fracture
Colon injury
Dental restoration failure
Ear canal abrasion
Ear injury
Exposure to communicable disease
Eye contusion
Femur fracture
Flail chest
Forearm fracture
Foreign body
Foreign body aspiration
Foreign body in eye
Hip fracture
InjuryLimb fracture
Limb traumatic amputation
Lip injury
Lumbar vertebral fracture
Maternal exposure during breast feeding
Mouth injury
Multiple injuries
Muscle contusion
Patella fracture
Pelvic fracture
Penis injury
Pharyngeal perforation
Post concussion syndrome
Post procedural discomfort

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)0001 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)
0
0
0
0
0
0
0
0
0
1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)000
000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)000
1 (0.0)01 (0.0)1 (0.0)01 (0.0)001 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Post procedural haemorrhage
Post procedural swelling
Postoperative ileus
Procedural haemorrhage
Procedural hypotension
Respiratory fume inhalation disorder
Scapula fracture
Scar
Soft tissue injury
Spinal column injury
Spinal cord injury cervical
Spinal fracture
Stab woundStoma site rash
Subdural haematoma
Sunburn
Tibia fracture
Toxicity to various agents
Traumatic haemothorax
Traumatic intracranial haemorrhage
Venom poisoning
Vulvovaginal injury
INVESTIGATIONS
Body temperature increased
Blood pressure increased
Blood glucose increased
Heart rate increased
Blood cholesterol increased
Low density lipoprotein increased
Blood thyroid stimulating hormone increased
Weight decreased
Blood glucose abnormal
Hepatic enzyme increased
High density lipoprotein increased
Mammogram abnormal
Prostatic specific antigen increased
Alanine aminotransferase increased

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)01 (0.0)001 (0.0)01 (0.0)1 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)1 (0.0)01 (0.0)001 (0.0)1 (0.0)0000
1 (0.0)001 (0.0)1 (0.0)01 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)172 (0.8)120 (0.5)
6 (0.0)8 (0.0)4 (0.0)5 (0.0)4 (0.0)3 (0.0)3 (0.0)1 (0.0)002 (0.0)1 (0.0)1 (0.0)(0.7, 0.9)
(0.5, 0.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

37 (0.2)
12 (0.1)
7 (0.0)1 (0.0)2 (0.0)01 (0.0)1 (0.0)01 (0.0)2 (0.0)2 (0.0)01 (0.0)0(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Blood chloride decreased
Blood creatinine decreased
Blood creatinine increased
Blood glucose fluctuation
Blood potassium decreased
Blood pressure diastolic increased
Blood pressure systolic increased
Blood sodium decreased
Blood testosterone decreased
Blood testosterone increased
Blood triglycerides increased
Body temperature
Body temperature decreased
C-reactive protein
Cardiac stress test abnormal
Electrocardiogram QT prolonged
Fractional exhaled nitric oxide increased
Glomerular filtration rate decreased
Heart rate irregularHepatitis C antibody positive
Herpes simplex test positive
Intraocular pressure increased
Mean cell volume decreased
Monocyte count increased
Platelet count increased
Respiratory rate increased
SARS-CoV-2 antibody test positive
Thyroid function test abnormal
Troponin increased
Urine ketone body present
Weight increased
White blood cell count increased
White blood cells urine positive0
1 (0.0)01 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)001 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)001 (0.0)01 (0.0)
0
0
0
0
0
0
0
0
0
0
1 (0.0)1 (0.0)01 (0.0)01 (0.0)000
1 (0.0)01 (0.0)01 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

METABOLISM AND NUTRITION DISORDERS
Decreased appetite
Type 2 diabetes mellitus
Vitamin D deficiency

100 (0.5)
39 (0.2)
8 (0.0)9 (0.0)(0.4, 0.6)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)

73 (0.3)
9 (0.0)8 (0.0)7 (0.0)(0.3, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Hypercholesterolaemia
Hyperlipidaemia
Hypokalaemia
Dyslipidaemia
Gout
Dehydration
Hyperglycaemia
Glucose tolerance impaired
Vitamin B12 deficiency
Diabetes mellitus inadequate control
Hypoglycaemia
Insulin resistanceHypertriglyceridaemia
Hypocalcaemia
Hypocholesterolaemia
Obesity
Polydipsia
Diabetes mellitus
Diabetic ketoacidosis
Fluid retention
Folate deficiency
Food intolerance
Hyperkalaemia
Hypernatraemia
Hyperuricaemia
Hypomagnesaemia
Hyponatraemia
Hypovolaemia
Impaired fasting glucose
Increased appetite
Iron deficiency
Lactic acidosis
MUSCULOSKELETAL AND CONNECTIVE TISSUEDISORDERS
Myalgia
Arthralgia
Pain in extremity

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

4 (0.0)6 (0.0)5 (0.0)4 (0.0)5 (0.0)2 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)00
0(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

9 (0.0)4 (0.0)5 (0.0)5 (0.0)2 (0.0)4 (0.0)3 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)01 (0.0)1 (0.0)
0
0
0
0
0
0
0
0
0
0
0
0
1 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1804 (8.2)(7.9, 8.6)

527 (2.4)(2.2, 2.6)

1239 (5.7)
268 (1.2)
185 (0.8)(5.3, 6.0)
(1.1, 1.4)
(0.7, 1.0)

168 (0.8)102 (0.5)
44 (0.2)(0.7, 0.9)
(0.4, 0.6)
(0.1, 0.3)

CONFIDENTIAL
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BNT162b2
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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Back pain
Neck pain
Muscle spasms
Osteoarthritis
Musculoskeletal stiffness
Tendonitis
Intervertebral disc protrusion
Bursitis
Muscular weakness
Musculoskeletal chest pain
Muscle contracture
Rotator cuff syndrome
Plantar fasciitis
Arthritis
Exostosis
Flank pain
Joint swelling
Joint stiffness
Musculoskeletal discomfort
Osteoporosis
Costochondritis
Joint range of motion decreased
Muscle fatigue
Muscle twitching
Musculoskeletal pain
Spinal osteoarthritis
Intervertebral disc degeneration
Limb discomfort
Pain in jaw
Synovial cyst
Tenosynovitis stenosans
Bone pain
Temporomandibular joint syndrome
Tendon disorder
Torticollis
Arthropathy
Axillary mass

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

97 (0.4)
29 (0.1)
27 (0.1)
11 (0.1)
12 (0.1)
10 (0.0)8 (0.0)10 (0.0)
10 (0.0)
10 (0.0)
4 (0.0)3 (0.0)4 (0.0)3 (0.0)5 (0.0)3 (0.0)2 (0.0)5 (0.0)4 (0.0)05 (0.0)5 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)3 (0.0)3 (0.0)3 (0.0)1 (0.0)3 (0.0)03 (0.0)1 (0.0)1 (0.0)1 (0.0)85 (0.4)
33 (0.2)
15 (0.1)
16 (0.1)
6 (0.0)7 (0.0)8 (0.0)5 (0.0)3 (0.0)3 (0.0)6 (0.0)7 (0.0)4 (0.0)4 (0.0)2 (0.0)4 (0.0)5 (0.0)1 (0.0)2 (0.0)6 (0.0)001 (0.0)2 (0.0)3 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)3 (0.0)03 (0.0)02 (0.0)1 (0.0)1 (0.0)(0.4, 0.5)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.3, 0.5)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Coccydynia
Fibromyalgia
Groin pain
Joint effusion
Metatarsalgia
Mobility decreased
Osteitis
Periarthritis
Psoriatic arthropathy
Spinal stenosis
Spondylitis
Synovitis
Trigger finger
Arthritis reactive
Bone swelling
Dupuytren's contractureIntervertebral disc disorder
Joint instability
Muscle discomfort
Muscle tightness
Osteochondritis
Osteochondrosis
Osteopenia
Rhabdomyolysis
Rheumatoid arthritis
Scoliosis
Spinal disorder
Systemic lupus erythematosus
Tendon pain
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED(INCL CYSTS AND POLYPS)
Basal cell carcinoma
LipomaUterine leiomyoma
Colon adenoma
Malignant melanoma
Breast cancer

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

2 (0.0)1 (0.0)1 (0.0)2 (0.0)02 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)000
1 (0.0)01 (0.0)1 (0.0)01 (0.0)0000
1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)01 (0.0)1 (0.0)02 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

32 (0.1)(0.1, 0.2)

36 (0.2)(0.1, 0.2)

3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

8 (0.0)5 (0.0)3 (0.0)2 (0.0)2 (0.0)3 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Prostate cancer
Acrochordon
Fibroadenoma of breast
Squamous cell carcinoma of skin
Adenocarcinoma gastric
Adenocarcinoma pancreas
Adenoma benign
Adrenal gland cancer
Benign breast neoplasm
Benign pancreatic neoplasm
Biliary cancer metastatic
Chondroma
Chronic myeloid leukaemia
Glomus tumour
Infected naevus
Intraductal proliferative breast lesion
Invasive ductal breast carcinoma
Leydig cell tumour of the testis
Lymphoproliferative disorder
Malignant melanoma of eyelid
Meningioma
Metastases to central nervous system
Metastases to liver
Oropharyngeal squamous cell carcinoma
Ovarian germ cell teratoma benign
Pancreatic carcinoma
Penile neoplasm
Penile squamous cell carcinoma
Prostate cancer metastatic
Seborrhoeic keratosis
Squamous cell carcinoma
Thyroid cancer
NERVOUS SYSTEM DISORDERS
HeadacheDizziness
Paraesthesia
Migraine

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

2 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)00000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)2 (0.0)2 (0.0)1 (0.0)000
000
1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)00000
1 (0.0)001 (0.0)0000
1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)1565 (7.1)
1339 (6.1)
78 (0.4)
22 (0.1)
24 (0.1)(6.8, 7.5)
(5.8, 6.4)
(0.3, 0.4)
(0.1, 0.2)
(0.1, 0.2)600 (2.7)424 (1.9)60 (0.3)
23 (0.1)
11 (0.1)(2.5, 3.0)
(1.8, 2.1)
(0.2, 0.4)
(0.1, 0.2)
(0.0, 0.1)

CONFIDENTIAL
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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Lethargy
Syncope
Sciatica
Dysgeusia
Somnolence
Tension headache
Presyncope
Hypoaesthesia
TremorBurning sensation
Parosmia
Subarachnoid haemorrhage
Carpal tunnel syndrome
Cervical radiculopathy
Disturbance in attention
Hyperaesthesia
Neuropathy peripheral
Sinus headache
Aphasia
Cerebrovascular accident
Dizziness postural
Facial paralysis
Migraine without aura
Nerve compression
Radiculopathy
Amnesia
Head discomfort
Ischaemic stroke
Mental impairment
Migraine with aura
Post herpetic neuralgia
Restless legs syndrome
Taste disorder
Transient ischaemic attack
Trigeminal neuralgia
Ageusia
Amyotrophic lateral sclerosis

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

25 (0.1)
11 (0.1)
11 (0.1)
12 (0.1)
9 (0.0)8 (0.0)8 (0.0)5 (0.0)6 (0.0)3 (0.0)5 (0.0)4 (0.0)1 (0.0)2 (0.0)4 (0.0)4 (0.0)1 (0.0)3 (0.0)2 (0.0)3 (0.0)2 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)000

6 (0.0)11 (0.1)
10 (0.0)8 (0.0)11 (0.1)
9 (0.0)5 (0.0)7 (0.0)6 (0.0)3 (0.0)1 (0.0)1 (0.0)3 (0.0)2 (0.0)003 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)00002 (0.0)1 (0.0)1 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Balance disorder
Cerebellar infarction
Cerebral atrophy
Cerebral capillary telangiectasia
Cerebral infarction
Cervicogenic headache
Depressed level of consciousness
Diabetic neuropathy
Drug withdrawal headache
Dyskinesia
Dystonia
Facial paresis
Generalised tonic-clonic seizure
Haemorrhagic stroke
Hemiplegic migraine
Hypersomnia
Hypogeusia
Hyposmia
Idiopathic intracranial hypertension
Motor dysfunction
Myoclonus
Nystagmus
Paraparesis
Parkinsonism
Periodic limb movement disorder
Peripheral sensory neuropathy
Piriformis syndrome
Sciatic nerve neuropathy
SeizureSpinal cord compression
Transient global amnesia
Uraemic encephalopathy
VIth nerve paralysis
PREGNANCY, PUERPERIUM AND PERINATAL
CONDITIONS
Abortion spontaneous
Abortion spontaneous incomplete

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)00000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)00000
1 (0.0)001 (0.0)1 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)01 (0.0)001 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

0(0.0, 0.0)

2 (0.0)(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

PRODUCT ISSUES
Device breakage
Device connection issue

1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

PSYCHIATRIC DISORDERS
Anxiety
Insomnia
Depression
Attention deficit hyperactivity disorder
Irritability
Panic attack
Anxiety disorder
Disorientation
Sleep disorder
Abnormal dreams
Depressed mood
Suicidal ideation
Alcohol withdrawal syndrome
Bipolar disorder
Bruxism
Mental disorder
Mental status changes
NightmareConfusional state
Depression suicidal
Dysphemia
Gastrointestinal somatic symptom disorder
Generalised anxiety disorder
Libido decreased
Libido increased
Listless
Mental fatigue
Mood swings
Panic disorder
Panic reaction
Paranoia
Post-traumatic stress disorder
Psychotic disorder

97 (0.4)
21 (0.1)
25 (0.1)
17 (0.1)
3 (0.0)4 (0.0)2 (0.0)2 (0.0)5 (0.0)4 (0.0)3 (0.0)1 (0.0)01 (0.0)01 (0.0)2 (0.0)2 (0.0)2 (0.0)00000
1 (0.0)1 (0.0)1 (0.0)0000
1 (0.0)1 (0.0)1 (0.0)(0.4, 0.5)
(0.1, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

75 (0.3)
24 (0.1)
8 (0.0)15 (0.1)
4 (0.0)2 (0.0)4 (0.0)3 (0.0)000
2 (0.0)3 (0.0)1 (0.0)2 (0.0)1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)000(0.3, 0.4)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)00
1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

RENAL AND URINARY DISORDERS
Nephrolithiasis
Dysuria
Haematuria
Acute kidney injury
Pollakiuria
Renal colic
Urinary retention
Bladder spasm
Chronic kidney disease
Costovertebral angle tenderness
Hydronephrosis
Micturition urgency
Nocturia
Obstructive nephropathy
Oedematous kidney
Perinephric oedema
Renal atrophy
Renal cyst haemorrhage
Subcapsular renal haematoma
Urethral discharge
Urinary bladder polyp
Urinary tract obstruction
Urine odour abnormal

34 (0.2)
6 (0.0)7 (0.0)4 (0.0)3 (0.0)5 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)0000
1 (0.0)001 (0.0)0(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

34 (0.2)
8 (0.0)4 (0.0)7 (0.0)5 (0.0)3 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Dysmenorrhoea
Erectile dysfunction
Ovarian cyst
Pelvic pain
Amenorrhoea
Benign prostatic hyperplasia
Breast pain

45 (0.2)
4 (0.0)1 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)4 (0.0)(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

39 (0.2)
3 (0.0)4 (0.0)1 (0.0)2 (0.0)2 (0.0)2 (0.0)0(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Restlessness
Schizophrenia
StressSubstance abuse
Suicide attempt

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Breast mass
Menorrhagia
Prostatitis
Vaginal haemorrhage
Breast cyst
Genital erythema
Haemorrhagic ovarian cyst
Menstruation delayed
Menstruation irregular
Metrorrhagia
Pruritus genital
Testicular pain
Uterine haemorrhage
Adenomyosis
Breast calcifications
Breast hyperplasia
Cervical dysplasia
Cervical polypDysfunctional uterine bleeding
Endometriosis
Haematospermia
Mammary duct ectasia
Menometrorrhagia
Nipple pain
Ovarian mass
Penile vein thrombosis
Polycystic ovaries
Postmenopausal haemorrhage
Premenstrual syndrome
Prostatomegaly
Scrotal pain
Uterine inflammation
Uterine prolapse
Vaginal discharge
Vulvovaginal pruritus
RESPIRATORY, THORACIC AND MEDIASTINALDISORDERS

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)1 (0.0)1 (0.0)02 (0.0)1 (0.0)02 (0.0)2 (0.0)1 (0.0)1 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)01 (0.0)2 (0.0)001 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)
0
0
0
0
0
0
0
0
1 (0.0)1 (0.0)1 (0.0)001 (0.0)001 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

194 (0.9)(0.8, 1.0)

168 (0.8)(0.7, 0.9)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Oropharyngeal pain
Nasal congestion
Cough
Rhinorrhoea
Rhinitis allergic
AsthmaDyspnoea
Throat irritation
Epistaxis
Upper-airway cough syndrome
Sinus congestion
Paranasal sinus discomfort
Pulmonary embolism
Sneezing
Chronic obstructive pulmonary disease
Dysphonia
Upper respiratory tract congestion
Bronchospasm
Dyspnoea exertional
Productive coughRespiratory tract congestion
Sleep apnoea syndrome
Wheezing
Acute respiratory failure
Asthma exercise induced
Dry throat
Pharyngeal swelling
Allergic sinusitis
Asthmatic crisis
Interstitial lung disease
Oropharyngeal discomfort
Pneumonia aspiration
Reflux laryngitis
Snoring
Allergic respiratory disease
Atelectasis
Emphysema

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

36 (0.2)
25 (0.1)
23 (0.1)
20 (0.1)
12 (0.1)
12 (0.1)
6 (0.0)6 (0.0)5 (0.0)6 (0.0)6 (0.0)4 (0.0)3 (0.0)3 (0.0)4 (0.0)2 (0.0)4 (0.0)3 (0.0)1 (0.0)2 (0.0)2 (0.0)3 (0.0)3 (0.0)2 (0.0)1 (0.0)3 (0.0)02 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)31 (0.1)
32 (0.1)
15 (0.1)
13 (0.1)
11 (0.1)
8 (0.0)10 (0.0)9 (0.0)8 (0.0)6 (0.0)5 (0.0)6 (0.0)5 (0.0)3 (0.0)1 (0.0)3 (0.0)1 (0.0)1 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)03 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)00(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Haemoptysis
Hiccups
Hypoxia
Lung infiltration
Nasal discomfort
Nasal obstruction
Nasal polyps
Nasal septum deviation
Nasal turbinate hypertrophy
Paranasal sinus hypersecretion
Pleurisy
Pleuritic pain
Pneumonitis
Pneumothorax
Pulmonary hypertension
Pulmonary mass
Pulmonary oedema
Pulmonary pain
Respiratory arrest
Rhinalgia
Rhinitis perennial
Sinus disorder
Tonsillar hypertrophy
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash
Pruritus
Hyperhidrosis
Dermatitis contact
Urticaria
Night sweats
Rash pruritic
Erythema
Alopecia
EczemaSkin lesion
Rash maculo-papular
Dermatitis

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)01 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)01 (0.0)
0
0
0
0
0
0
0
1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)1 (0.0)0000
1 (0.0)001 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)224 (1.0)
54 (0.2)
23 (0.1)
31 (0.1)
14 (0.1)
15 (0.1)
17 (0.1)
7 (0.0)9 (0.0)5 (0.0)6 (0.0)3 (0.0)5 (0.0)4 (0.0)(0.9, 1.2)
(0.2, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

158 (0.7)
41 (0.2)
18 (0.1)
9 (0.0)19 (0.1)
12 (0.1)
3 (0.0)5 (0.0)2 (0.0)4 (0.0)3 (0.0)6 (0.0)3 (0.0)3 (0.0)(0.6, 0.8)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Dermatitis allergic
Angioedema
Dermal cyst
Rash erythematous
Actinic keratosis
Blister
Ecchymosis
Hand dermatitis
PapulePsoriasis
Rash papular
Acne
Alopecia areata
Cold sweat
Diabetic footDrug eruption
MaculePain of skin
Pityriasis rosea
Pruritus allergic
Rosacea
Seborrhoeic dermatitis
Skin mass
Dermatitis acneiform
Dermatitis bullous
Dermatitis exfoliative
Dyshidrotic eczema
Fixed eruption
Hangnail
Hidradenitis
Ingrowing nail
Livedo reticularis
Mechanical urticaria
Onychomadesis
Pityriasis
Pseudofolliculitis
Skin discolouration

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

3 (0.0)3 (0.0)4 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)3 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)3 (0.0)2 (0.0)1 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)02 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)01 (0.0)01 (0.0)000
1 (0.0)01 (0.0)0000(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)01 (0.0)1 (0.0)00
0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)001 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SOCIAL CIRCUMSTANCES
MenopauseHigh risk sexual behaviour

3 (0.0)2 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)000(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SURGICAL AND MEDICAL PROCEDURES
Tooth extraction
Dental implantation
Wisdom teeth removal
Dental care
Endodontic procedure
Abortion induced
Apicectomy
Botulinum toxin injection
Cardiac pacemaker replacement
Carpal tunnel decompression
Cataract operation
Drug titration
Facet joint block
Gingival operation
Inguinal hernia repair
Lacrimal duct procedure
Lens extraction
Medical device implantation
Open reduction of fracture
Postoperative care
Rhinoplasty
Sclerotherapy
Skin neoplasm excision
Toe operation
Vasectomy
Wound drainage

28 (0.1)
6 (0.0)5 (0.0)2 (0.0)02 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)001 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

19 (0.1)
6 (0.0)2 (0.0)2 (0.0)2 (0.0)01 (0.0)0000
1 (0.0)00000
1 (0.0)1 (0.0)001 (0.0)001 (0.0)1 (0.0)0(0.1, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS

83 (0.4)(0.3, 0.5)

82 (0.4)(0.3, 0.5)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Skin induration
Skin irritation
Skin ulcer
Stasis dermatitis
Urticaria contact
Urticaria papular

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Table 6.

Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 1 Month After Dose 2, by System Organ Class and Preferred Term –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Hypertension
Hot flush
Flushing
Deep vein thrombosis
Haematoma
Hypotension
Orthostatic hypotension
Varicose vein
Aortic aneurysm
Arteriosclerosis
Hypertensive crisis
Hypertensive urgency
Accelerated hypertension
Aortic dilatation
Aortic stenosis
Diastolic hypertension
Essential hypertension
Intermittent claudication
Lymphoedema
Lymphorrhoea
PallorPhlebolith
Raynaud's phenomenon
Subgaleal haematoma

BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

42 (0.2)
7 (0.0)11 (0.1)
5 (0.0)4 (0.0)4 (0.0)1 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)001 (0.0)1 (0.0)01 (0.0)0000

46 (0.2)
9 (0.0)2 (0.0)3 (0.0)4 (0.0)3 (0.0)2 (0.0)1 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

(0.2, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:09)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s130 all pd2 p3 saf

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2.7.4.2.4.2.1.2.1.1. Participants with Confirmed Stable HIV Disease: Blinded PlaceboControlled Follow-Up Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study
C4591001, Adverse Events by System Organ Class and Preferred Term)
From Dose 1 to 1 month after Dose 2, and similar to the overall population, most AEs
reported for the subset of 200 HIV-positive participants from Dose 1 to 1 month after Dose 2were in SOCs with reactogenicity events. There were few AEs reported: 26 (26%) in the
BNT162b2 group and 13 (13%) in the placebo group.






general disorders and administration site conditions (19.0% BNT162b2 vs 2.0%
placebo)musculoskeletal and connective tissue disorders (6.0% BNT162b2 vs 3.0% placebo)
nervous system disorders (5.0% BNT162b2 vs 0.0% placebo)
gastrointestinal disorders (3.0% BNT162b2 vs 4.0% placebo)
infections and infestations (2.0% BNT162b2 vs 2.0% placebo)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

2.7.4.2.4.2.1.2.2. Related Adverse Events by System Organ Class and Preferred Term:
Blinded Placebo-Controlled Follow-Up Period From Dose 1 to 1 Month After Dose 2(Phase 3, Study C4591001, Analysis of Adverse Events)
Details and outputs regarding related AEs for Phase 3 of Study C4591001 are in Module
5.3.5.1 C4591001 6-Month Update CSR Section 12.2.3.1.2.2.
From Dose 1 to 1 month after Dose 2, AEs assessed as related by the investigator during theblinded placebo-controlled follow-up period were reported by 23.9% of participants in the
BNT162b2 group and 6.0% of participants in the placebo group (Table 5). Most related AEs
were reactogenicity events and in the SOC of general disorders and administration site
conditions, reported by 4650 (21.2%) BNT162b2 recipients and 883 (4.0%) placebo
recipients. Among the BNT162b2 participants who had AEs of lymphadenopathy, 62 of 83
participants had events assessed by the investigator as related to study intervention; themajority of lymphadenopathy events occurred in the arm and neck region and were reported
within 1 to 4 days after vaccination (Section 2.7.4.2.4.3.4.1.3).
2.7.4.2.4.2.1.2.3. Immediate Adverse Events: Blinded Placebo Controlled Follow-Up
Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study C4591001, Analysis ofAdverse Events)
Details and outputs regarding immediate AEs for Phase 3 of Study C4591001 are in Module
5.3.5.1 C4591001 6-Month Update CSR Section 12.2.3.1.2.3.
After Dose 1, participants with immediate AEs were low in frequency (≤0.5%). Most
immediate AEs after Dose 1 were in the SOC of general disorders and administration site
conditions, primarily injection site reactions in the BNT162b2 versus placebo groups, with
injection site pain (0.3% vs 0.2%) most frequently reported.
After Dose 2, participants with immediate AEs were low in frequency (0.3%). Most
immediate AEs after Dose 2 were in the SOC of general disorders and administration site
conditions, primarily injection site reactions, in the BNT162b2 versus placebo groups with
injection site pain (0.2% vs 0.1%) most frequently reported.
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2.7.4.2.4.2.1.2.4. Severe or Life-Threatening Adverse Events: Blinded Placebo
Controlled Follow-Up Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study
C4591001, Analysis of Adverse Events)
Details and outputs regarding severe or life-threatening AEs for Phase 3 of Study C4591001
are in Module 5.3.5.1 C4591001 6-Month Update CSR Section 12.2.3.1.2.4.
From Dose 1 to 1 month after Dose 2, severe AEs reported during the blinded follow-up
period were low in frequency, reported in 1.2% of BNT162b2 recipients and 0.7% of placebo
recipients. Severe events were concentrated in the SOCs of general disorders andadministration site conditions, generally reflecting terms consistent with reactogenicity, in
the BNT162b2 versus placebo groups (0.4% vs 0.0%).
There were 21 participants (0.1%) in the BNT162b2 group and 26 participants (0.1%) in theplacebo group who had at least 1 life-threatening AE from Dose 1 to 1 month after Dose 2.
None of the life-threatening AEs were assessed by the investigator as related to study
intervention.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)No clinically meaningful differences were observed for severe or life-threatening AEs by age
group.
2.7.4.2.4.2.2. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to the
Unblinding Date (Phase 3, Study C4591001)
2.7.4.2.4.2.2.1. Summary of Adverse Events: Blinded Placebo-Controlled Follow-Up
Period From Dose 1 to the Unblinding Date (Phase 3, Study C4591001)
An overview of AE incidence rates adjusted for exposure time from Dose 1 to the unblinding
date for 43,847 participants during the blinded placebo-controlled follow-up (including thoseanalyzed in Phase 2) is presented in Table 7. The IRs/100 PY for participants who reported atleast 1 AE were 83.2 in the BNT162b2 group and 43.4 in the placebo group, and IRs for
related AEs were 62.9 in the BNT162b2 group and 16.0 in the placebo group.
IRs of severe AEs, SAEs, and AEs leading to withdrawal were ≤4.3, ≤3.3, and ≤0.6 per
100 PY, respectively, in both groups. IRs for discontinuations because of related AEs were
0.2 per 100 PY in the BNT162b2 group and 0.1 per 100 PY in the placebo group.
From Dose 1 to the unblinding date, there were 15 (0.2 per 100 PY) deaths in the BNT162b2
group and 14 (0.2 per 100 PY) deaths in the placebo group.
In the younger age group, the IRs for of participants who reported at least 1 AE from Dose 1
to the unblinding date were 88.4 per 100 PY and 43.5 per 100 PY in the BNT162b2 andplacebo groups, respectively. In the older age group, the IRs for participants who reported atleast 1 AE from Dose 1 to the unblinding date were 75.7 per 100 PY and 43.3 per 100 PY in
the BNT162b2 and placebo groups, respectively.

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Table 7.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR (/100 PY)d(95% CIe)nc

Placebo(Na=21921, TEb=82.2)
IR (/100 PY)d(95% CIe)

Adverse Eventnc

Any event
Relatedf
SevereLife-threatening
Any serious adverse event
Relatedf
SevereLife-threatening
Any adverse event leading towithdrawal
Relatedf
SevereLife-threatening
Death

6947
5246
356
48
268
4
148
48
45

83.2
62.9
4.3
0.6
3.2
0.0
1.8
0.6
0.5

(81.3, 85.2)(61.2, 64.6)(3.8, 4.7)
(0.4, 0.8)
(2.8, 3.6)
(0.0, 0.1)
(1.5, 2.1)
(0.4, 0.8)
(0.4, 0.7)

3568
1313
256
54
268
1
156
54
51

43.4
16.0
3.1
0.7
3.3
0.0
1.9
0.7
0.6

(42.0, 44.9)(15.1, 16.9)(2.7, 3.5)
(0.5, 0.9)
(2.9, 3.7)
(0.0, 0.1)
(1.6, 2.2)
(0.5, 0.9)
(0.5, 0.8)

13
10
15
15

0.2
0.1
0.2
0.2

(0.1, 0.3)
(0.1, 0.2)
(0.1, 0.3)
(0.1, 0.3)

12
12
16
14

0.1
0.1
0.2
0.2

(0.1, 0.3)
(0.1, 0.3)
(0.1, 0.3)
(0.1, 0.3)

a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number ofsubjects reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:11)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s092 all unb p3 saf

Subgroup Analyses
In the BNT162b2 group, there were 674 baseline SARS-CoV-2 positive and 21102 baseline
SARS-CoV-2 negative participants, and there were 705 baseline SARS-COV-2 positive and21092 SARS-CoV-2 negative participants in the placebo group. Similar to what wasobserved in the overall AE analysis irrespective of baseline status (Table 7), IRs of at least
1 AE in the baseline SARS-CoV-2 positive subgroup were 70.7 per 100 PY in the
BNT162b2 group and 31.9 per 100 PY in the placebo group, and IRs of at least 1 AE in thebaseline SARS-CoV-2 negative subgroup were 83.6 per 100 PY in the BNT162b2 group and43.8 per 100 PY in the placebo group. IRs of related AEs in the BNT162b2 group were 51.8
per 100 PY (baseline positive) and 63.2 per 100 PY (baseline negative). The IRs of SAEs,
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related SAEs, severe SAEs, and life threatening SAEs were similar in the BNT162b2 andplacebo groups, which support these events are not increased in baseline positive
participants. Given the differences in exposure (2.5 vs 80.4) by baseline SARS-CoV-2
positive and negative status, respectively, direct comparisons should be interpreted withcaution. See Section 2.7.4.2.4.2.2.2 for subgroup analyses of SOCs by baseline status, which
supports that there is no evidence that individuals who are positive at baseline report AEs at ahigher rate than those who are negative at baseline.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The IR of any AEs and related AEs were similar in those positive and negative at baseline,with the IR for any AE of 70.7 per 100 PY (95% CI: 60.7, 81.9) and 83.6 per 100 PY (95%
CI: 81.7, 85.7) and for related AE of 51.8 per 100 PY (95% CI: 43.3, 61.4) and 63.2 per 100
PY (95% CI:61.5, 65.0), respectively. The IR for SAEs was 4.0 per 100 PY (95% CI: 1.9,
7.3) (baseline positive) and 3.2 per 100 PY (95% CI: 2.8, 3.6) (baseline negative), however
none of the SAEs in the positive baseline group were related to BNT162b2, as assessed by
the investigator. The death rate was also similar: 0.8 per 100 PY (95% CI: 0.1, 2.9) (baseline
positive) and 0.2 per 100 PY (95 CI: 0.1, 0.3) (baseline negative).
IRs of at least 1 AE in the BNT162b2 group were 78.4 per 100 PY (95% CI: 74.9, 82.0;
n=5684) in Hispanic/Latino and 85.4 per 100 PY (95% CI: 83.1, 87.8; n=16131) in NonHispanic/Non-Latino participants. The IRs of SAEs, AEs leading to withdrawal, and death
were similar in the Hispanic/Latino and Non-Hispanic/Non-Latino groups. None of the SAEs
were considered related to BNT162b2 in the Hispanic/Latino group.
IRs of at least 1 AE in the BNT162b2 group were lower in Black or African American
participants (53.5 per 100 PY) compared with White (83.1 per 100 PY) or All Others (120.1
per 100 PY). Other IRs were similar in the groups.
IRs of at least 1 AE in the BNT162b2 group were greater in females (91.0 per 100 PY[95% CI: 88.1, 94.0] than males (76.0 per 100 PY [95% CI: 73.4, 78.6]); that cannot be
accounted for by the rates in placebo for females (46.8 [95% CI: 44.7, 49.0]) and males (40.1[95% CI: 38.2, 42.1]). IRs for related and severe AEs were also greater in females (68.6 per
100 PY [95% CI: 66.1, 71.2] and 4.9 per 100 PY [95% CI: 4.2, 5.6], respectively) than inmales (57.5 per 100 PY [95% CI: 55.3, 59.8] and 3.7 per 100 PY [95% CI: 3.2, 4.3],
respectively). However, life threatening AEs, SAEs, related SAEs, severe SAEs, life
threatening SAEs and death IR were similar in males and females.
2.7.4.2.4.2.2.1.1. Participants with Confirmed Stable HIV Disease: Blinded PlaceboControlled Follow-Up Period From Dose 1 to the Unblinding Date (Phase 3, Study
C4591001, Summary of Adverse Events)
The subset of 200 HIV-positive participants during the blinded placebo-controlled follow-up
period showed generally similar trends as the overall population. The IRs for HIV-positive
participants who reported at least 1 AE and at least 1 related AE were 95.8 per 100 PY and62.8 per 100 PY, respectively, for the BNT162b2 group and 52.0 per 100 PY and 10.4 per
100 PY, respectively, for the placebo group. There were 2 SAEs in the BNT162b2 group (1severe and 1 life-threatening) and 2 SAEs in the placebo group (1 life-threatening). There
were 2 AEs leading to withdrawal in the BNT162b2 group (1 life-threatening) and 1 AE
(life-threatening) leading to withdrawal in the placebo group. There were 2 deaths, 1 each in
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the BNT162b2 and placebo groups; neither were assessed by the investigator as related to
study intervention (see Section 2.7.4.2.4.3.1).
2.7.4.2.4.2.2.2. Analysis of Adverse Events: Blinded Placebo-Controlled Follow-Up
Period From Dose 1 to the Unblinding Date (Phase 3, Study C4591001)
2.7.4.2.4.2.2.2.1. Adverse Events by System Organ Class and Preferred Term: Blinded
Placebo-Controlled Follow-Up Period From Dose 1 to the Unblinding Date (Phase 3,
Study C4591001, Analysis of Adverse Events)
Incidence rates of AEs from Dose 1 to the unblinding date during the blinded placebocontrolled follow-up period are presented in Table 7. Results were similar to the Dose 1 to
1 month after Dose 2 follow-up period.
From Dose 1 to the unblinding date, the most common AEs by IRs were reactogenicity
events and were reported at higher IRs in the BNT162b2 group than in the placebo group:

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)general disorders and administration site conditions (56.9 per 100 PY BNT162b2 vs12.3 per 100 PY placebo)
musculoskeletal and connective tissue disorders (22.3 per 100 PY BNT162b2 vs 7.6
per 100 PY placebo)
nervous system disorders (19.2 per 100 PY BNT162b2 vs 7.7 per 100 PY placebo)
gastrointestinal disorders (9.0 per 100 PY BNT162b2 vs 6.2 per 100 PY placebo)

In the younger versus older BNT162b2 age groups, AE IRs in these SOCs were:general disorders and administration site conditions (63.7 per 100 PY vs 46.9 per
100 PY)musculoskeletal and connective tissue disorders (24.6 per 100 PY vs 18.8 per
100 PY)
nervous system disorders (21.8 per 100 PY vs 15.3 per 100 PY)
gastrointestinal disorders (9.5 per 100 PY vs 8.2 per 100 PY)

The higher rates of AEs in these SOC is consistent with the reactogenicty analysis showing
higher rates of reactogenicty in the younger age group. AEs with the highest IRs in the
BNT162b2 group by PT overall were injection site pain (35.0 per 100 PY), pyrexia (18.2 per
100 PY), fatigue (17.6 per 100 PY), chills (16.4 per 100 PY), headache (16.2 per 100 PY),
and myalgia (14.9 per 100 PY).
The IR of AEs in the SOC of investigations was higher in the BNT162b2 group (2.2 per 100
PY) than in the placebo group (0.6 per 100 PY) mainly due to the higher IR of bodytemperature increased in the BNT162b2 group (IR of 1.5 per 100 PY vs 0.2 per 100 PY for
the placebo group).
Cases of night sweats and hyperhidrosis are discussed in Section 2.7.4.2.4.2.1.2.1 (most werereported within 7 days after Dose 1 or 2).

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In the nervous systems disorder SOC, there were 4 participants who reported facial paralysis
in the BNT162b2 group (compared to 1 in the placebo group). There was an additional caseof facial paresis in the placebo group. Hence there were 4 cases of facial paralysis/paresis in
the in the BNT162b2 group and 2 in the placebo group. See Section 2.7.4.2.4.3.4.1.2.
There was 1 case of COVID-19 pneumonia (reported in the BNT162b2 group) which led todeath (Table 16). This participant was diagnosed based on a local COVID-19 test that was
not protocol-approved and was not confirmed by a test result from the central laboratory.
Therefore, this participant was not included in efficacy analyses.
Among the AEs of lymphadenopathy in the BNT162b2 group, the majority (62 of
87 participants; [0.7 per 100 PY]) were assessed by the investigator as related to study
intervention. Most cases occurred in the arm and neck region and were reported within 1 to 4
days after vaccination (Section 2.7.4.2.4.3.4.1.3).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The IRs for hepatobiliary disorders was 0.3 per 100 PY and 0.2 per 100 PY in the BNT162b2
and placebo group, respectively. There were 24 participants in the BNT162b2 group who had
AEs in the SOC of hepatobiliary disorders compared to 16 participants in the placebo group.
Narratives for these cases are provided (see Section 2.7.4.2.4.4).
A total of 11 cases of reported PTs associated with deafness in the blinded placebo-controlled
follow-up period through the unblinding date included: Deafness, Deafness unilateral,
Deafness neurosensory, Hypoacusis, and Sudden hearing loss. Six participants wererandomized to the BNT162b2 group (age range 43 to 65 years of age), and 5 participants
were randomized to placebo (age range 36 to 74 years of age). For 1 participant in eachgroup, onset was 19 days after Dose 1. Onset ranged from 1 to 55 days after Dose 2 for
5 participants in the BNT162b2 and ranged from 2 to 94 days after Dose 2 for 4 participantsin the placebo group. The duration ranged from 9 to 155 days after AE onset with 4 eventsstill ongoing at the time of data cutoff (13 March 2021). The toxicity grades were mostly
mild (4 in the BNT162b2 group, and 2 in placebo) or moderate (1 in the BNT162b2 group,and 3 in placebo), with one being severe (BNT162b2 group). In the BNT162b2 group,
2 events were deemed related to study vaccine by the investigator. None of the reported
events were SAEs.
Other events of clinical interest that were identified by the sponsor and/or from the CDC listof AESIs are discussed in Section 2.7.4.2.4.3.4.

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Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

System Organ Class
Preferred Termnc

Any event

6947

83.2

(81.3, 85.2)

3568

43.4

(42.0, 44.9)

BLOOD AND LYMPHATIC SYSTEMDISORDERS
Anaemia
Blood loss anaemia
Coagulopathy
Hypochromic anaemia
Iron deficiency anaemia
Leukocytosis
Leukopenia
Lymph node pain
Lymphadenitis
Lymphadenopathy
Lymphadenopathy mediastinal
Lymphocytosis
Lymphopenia
Microcytic anaemia
Monoclonal B-cell lymphocytosis
Neutropenia
Splenomegaly
Thrombocytopenia
Thrombocytosis

118

1.4

(1.2, 1.7)

32

0.4

(0.3, 0.5)

8
2
1
1
9
0
3
7
1
87
1
1
1
0
0
2
0
1
0

0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
1.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.8, 1.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

10
1
0
0
5
2
0
1
0
8
1
0
0
1
1
1
1
2
2

0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CARDIAC DISORDERS
Acute coronary syndrome
Acute left ventricular failure
Acute myocardial infarction
Angina pectoris
Angina unstable
Aortic valve incompetence
Arrhythmia
Arrhythmia supraventricular
Arteriosclerosis coronary artery
Arteriospasm coronary
Atrial fibrillation
Atrial flutter
Atrioventricular block complete

87
1
1
6
5
2
0
1
1
0
1
13
0
1

1.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0

(0.8, 1.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)

78
4
0
4
1
3
2
3
0
1
1
17
2
1

0.9
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0

(0.8, 1.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)

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Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Atrioventricular block first degree
Bradycardia
Bundle branch block left
Bundle branch block right
Cardiac arrest
Cardiac disorder
Cardiac failure acute
Cardiac failure congestive
Cardio-respiratory arrest
Cardiomegaly
Cardiovascular disorder
Coronary artery disease
Coronary artery dissection
Coronary artery occlusion
Hypertensive heart disease
Junctional ectopic tachycardia
Left atrial enlargement
Left ventricular dysfunction
Left ventricular hypertrophy
Mitral valve incompetence
Mitral valve prolapse
Myocardial infarction
Myocardial ischaemia
Myocarditis
Palpitations
Pericardial effusion
Pericarditis
Postural orthostatic tachycardia syndrome
Sinus bradycardia
Sinus tachycardia
Supraventricular tachycardia
Tachyarrhythmia
Tachycardia
Tricuspid valve incompetence
Ventricular arrhythmia
Ventricular extrasystoles
Ventricular tachycardia

1
3
0
1
6
1
0
5
1
1
1
6
1
0
1
0
0
1
2
1
1
4
2
0
7
0
1
0
0
1
1
0
15
1
1
2
2

0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
2
1
0
2
0
1
3
1
0
0
6
0
1
0
1
1
0
1
3
1
8
0
1
16
1
0
1
1
1
1
1
7
1
0
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONGENITAL, FAMILIAL AND GENETICDISORDERS

40.0(0.0, 0.1)

5

0.1

(0.0, 0.1)

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Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Arnold-Chiari malformation
Congenital bladder neck obstruction
Congenital cystic kidney disease
Congenital ureteropelvic junction obstruction
Developmental hip dysplasia
Gastrointestinal arteriovenous malformation
Heart disease congenitalProtein S deficiency
Type V hyperlipidaemianc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
0
1
0
0
1
1
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

1
1
0
1
1
0
0
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

EAR AND LABYRINTH DISORDERS
Allergic otitis media
Cerumen impaction
Deafness
Deafness neurosensory
Deafness unilateral
Ear discomfort
Ear disorder
Ear pain
Ear pruritus
Eustachian tube dysfunction
Hyperacusis
Hypoacusis
Meniere's disease
Otorrhoea
Sudden hearing loss
Tinnitus
Tympanic membrane perforation
VertigoVertigo positional

76
0
3
0
2
3
3
0
13
0
1
1
0
1
1
1
9
0
31
8

0.9
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.4
0.1

(0.7, 1.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.3, 0.5)
(0.0, 0.2)

61
1
1
2
0
1
1
2
11
1
1
0
2
1
0
0
11
1
26
4

0.7
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.3
0.0

(0.6, 1.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)

ENDOCRINE DISORDERS
Autoimmune thyroiditis
GoitreHyperprolactinaemia
Hyperthyroidism
Hypogonadism
Hypothyroidism
Oestrogen deficiency
Thyroid cyst

17
1
1
1
1
2
8
1
0

0.2
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)

11
1
0
0
0
0
8
0
1

0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Thyroid mass
EYE DISORDERS
Amaurosis fugax
Angle closure glaucoma
Asthenopia
Astigmatism
Blepharitis
Blepharospasm
Blindness unilateral
Cataract
Chalazion
Choroidal neovascularisation
Conjunctival haemorrhage
Conjunctival hyperaemia
Conjunctival oedema
Conjunctivitis allergic
Corneal irritation
Dacryostenosis acquired
Diabetic retinopathy
Diplopia
Dry age-related macular degeneration
Dry eyeEpiscleritis
Eye allergy
Eye haemorrhage
Eye inflammation
Eye irritation
Eye painEye pruritus
Eye swelling
Eyelid haematoma
Eyelid oedema
Eyelid pain
Eyelids pruritus
Glaucoma
Hypermetropia
Iritis
Keratitisnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

3

0.0

(0.0, 0.1)

1

0.0

(0.0, 0.1)

70
0
1
1
0
2
0
1
7
3
1
1
0
0
3
1
0
0
2
0
1
1
0
0
0
6
7
2
0
0
1
1
1
2
0
0
1

0.8
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.7, 1.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

65
1
0
1
1
2
2
0
8
2
0
4
1
1
2
0
1
1
0
1
6
0
1
1
1
3
4
1
1
1
0
0
0
2
1
1
4

0.8
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.6, 1.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Lacrimation increased
Macular oedema
Ocular discomfort
Ocular hyperaemia
Ophthalmic vein thrombosis
Photophobia
Retinal artery occlusion
Retinal detachment
Retinal tear
Scleral discolouration
Swelling of eyelid
Ulcerative keratitis
Uveitis
Vision blurred
Visual acuity reduced
Visual impairment
Vitreous detachment
Vitreous floaters
GASTROINTESTINAL DISORDERS
Abdominal adhesions
Abdominal discomfort
Abdominal distension
Abdominal hernia
Abdominal pain
Abdominal pain lower
Abdominal pain upper
Abdominal rigidity
Abnormal faeces
Acute abdomen
Anal pruritus
Angular cheilitis
Aphthous ulcer
Appendix disorder
Cheilitis
Chronic gastritis
Coeliac artery aneurysm
Coeliac disease
Colitisnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

2
2
0
3
1
2
1
2
1
1
1
2
0
7
1
1
4
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

1
0
1
2
0
1
1
3
0
0
0
1
1
2
0
1
2
2

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

748
1
6
7
1
23
3
27
1
0
0
0
1
9
0
1
0
0
1
2

9.0
0.0
0.1
0.1
0.0
0.3
0.0
0.3
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0

(8.3, 9.6)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

511
0
5
3
2
22
4
15
0
1
1
1
0
3
1
2
1
1
0
1

6.2
0.0
0.1
0.0
0.0
0.3
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(5.7, 6.8)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Colitis ischaemic
Colitis microscopic
Colitis ulcerative
Constipation
Crohn's disease
Dental caries
Diarrhoea
Diverticular perforation
Diverticulum
Diverticulum intestinal
Diverticulum intestinal haemorrhagic
Dry mouth
Duodenal obstruction
Duodenal ulcer
Dyspepsia
Dysphagia
Enterocolitis
Epiploic appendagitis
Eructation
Faeces soft
Femoral hernia
Flatulence
Food poisoning
Frequent bowel movements
Gastric antral vascular ectasia
Gastric polyps
Gastric ulcer
Gastric ulcer haemorrhage
Gastritis
Gastritis erosive
Gastrointestinal disorder
Gastrointestinal haemorrhage
Gastrointestinal mucosa hyperaemia
Gastrointestinal pain
Gastrointestinal sounds abnormal
Gastrooesophageal reflux disease
Gingival bleeding
Gingival discomfort
Gingival pain

nc

0
3
1
10
1
10
255
0
4
1
1
2
1
0
15
3
1
1
1
1
1
5
3
0
1
0
1
1
5
1
3
2
0
1
0
15
0
1
3

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.0
0.1
3.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.1, 0.2)
(2.7, 3.5)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

1
0
2
13
0
8
189
1
1
4
0
4
0
1
14
2
0
0
1
2
0
3
1
1
0
1
1
0
14
0
1
1
1
0
1
23
1
1
0

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.2
0.0
0.1
2.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.2)
(2.0, 2.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Gingival swelling
Glossitis
Glossodynia
Haematemesis
Haematochezia
Haemorrhoidal haemorrhage
Haemorrhoids
Hiatus hernia
Hypoaesthesia oralHypoaesthesia teeth
Ileus
Impaired gastric emptying
Incarcerated inguinal hernia
Inguinal hernia
Internal hernia
Intestinal obstruction
Intestinal perforation
Intestinal polyp
Intestinal strangulation
Intra-abdominal fluid collection
Irritable bowel syndrome
Large intestine perforation
Large intestine polypLip oedema
Lip swelling
Loose tooth
Mouth ulceration
NauseaNoninfective gingivitis
Obstructive pancreatitis
Odynophagia
Oesophageal food impaction
Oesophageal spasm
Oesophageal ulcer
Oesophageal varices haemorrhage
Oesophagitis
Oral discomfort
Oral lichenoid reaction
Oral mucosa haematoma

nc

0
1
2
0
3
1
5
4
1
1
0
2
1
1
1
1
1
1
1
1
5
0
4
1
2
0
0
277
2
1
13
0
1
1
0
0
1
1
0

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
3.3
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(2.9, 3.7)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

nc

1
0
0
1
0
0
11
3
2
0
1
0
0
5
0
1
0
0
0
0
3
1
5
0
1
1
2
88
0
0
8
1
0
1
1
2
0
0
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
1.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.9, 1.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Oral pain
Palatal disorder
Pancreatic cyst
Pancreatic failure
Pancreatitis
Pancreatitis acute
Paraesthesia oral
Parotid duct obstruction
Peptic ulcer
Precancerous lesion of digestive tract
Proctalgia
Rectal haemorrhage
Rectal polyp
Retching
Retroperitoneal haematoma
Salivary gland calculus
Salivary gland mucocoele
Small intestinal obstruction
Stomatitis
Swollen tongue
Teething
Tongue discolouration
Tongue discomfort
Tongue oedema
Tongue pruritus
Tongue ulceration
Tooth disorder
Tooth impacted
ToothacheUmbilical hernia
Varices oesophageal
Volvulus
Vomiting

2
0
0
0
1
1
2
1
1
0
1
2
1
3
0
0
0
4
2
2
0
0
0
1
1
1
0
1
26
1
1
0
68

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.0
0.8

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.6, 1.0)

0
1
1
1
2
3
2
1
0
1
1
1
0
1
1
2
1
3
3
1
1
1
1
0
0
0
1
2
28
4
0
1
35

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.0
0.4

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.3, 0.6)

GENERAL DISORDERS AND
ADMINISTRATION SITE CONDITIONSAdverse drug reaction
Application site erythema
Application site pain
Application site pruritus

4748

56.9

(55.3, 58.5)

1010

12.3

(11.5, 13.1)

3
1
2
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
0
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

System Organ Class
Preferred Termnc

Application site rash
Application site reaction
Asthenia
Axillary pain
Capsular contracture associated with breast
implant
Chest discomfort
Chest pain
ChillsChronic fatigue syndrome
Cyst
Death
Discomfort
Drug withdrawal syndrome
Effusion
Exercise tolerance decreased
Face oedema
Facial pain
Fatigue
Feeling abnormal
Feeling cold
Feeling hot
Gait disturbanceIllness
Induration
Inflammation
Influenza like illness
Injection site bruising
Injection site dermatitis
Injection site discolouration
Injection site discomfort
Injection site erythema
Injection site haematoma
Injection site haemorrhage
Injection site hyperaesthesia
Injection site induration
Injection site injury
Injection site irritation
Injection site lymphadenopathy

0
1
77
14
0

0.0
0.0
0.9
0.2
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.7, 1.2)
(0.1, 0.3)
(0.0, 0.0)

1
0
25
3
1

0.0
0.0
0.3
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)

5
17
1368
0
2
0
1
2
0
1
2
1
1466
3
2
8
0
2
1
1
24
13
1
2
6
185
2
3
1
10
0
1
1

0.1
0.2
16.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
17.6
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.3
0.2
0.0
0.0
0.1
2.2
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.1, 0.3)
(15.5, 17.3)(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(16.7, 18.5)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(1.9, 2.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

5
16
121
1
1
1
0
0
1
0
0
0
379
0
0
1
1
0
0
0
4
18
0
1
3
29
4
3
0
4
1
0
0

0.1
0.2
1.5
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
4.6
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.1, 0.3)
(1.2, 1.8)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(4.2, 5.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

System Organ Class
Preferred Termnc

Injection site macule
Injection site mass
Injection site nodule
Injection site oedema
Injection site pain
Injection site papule
Injection site paraesthesia
Injection site plaqueInjection site pruritus
Injection site rash
Injection site reaction
Injection site swelling
Injection site urticaria
Injection site warmth
Injury associated with device
MalaiseMass
Medical device pain
Medical device site granuloma
Mucosal disorderMultiple organ dysfunction syndrome
NoduleNon-cardiac chest pain
Oedema peripheral
Pain
Peripheral swelling
Pyrexia
Sensation of foreign body
Shoulder injury related to vaccine
administration
Sluggishness
Sudden cardiac death
Swelling
Swelling faceTemperature intolerance
Therapeutic response unexpected
ThirstVaccination site induration
Vaccination site pain

1
3
3
12
2917
3
2
0
38
2
5
140
1
14
0
130
0
2
0
0
0
0
6
8
628
8
1520
3
1

0.0
0.0
0.0
0.1
35.0
0.0
0.0
0.0
0.5
0.0
0.1
1.7
0.0
0.2
0.0
1.6
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1
7.5
0.1
18.2
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(33.7, 36.2)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.3, 0.6)
(0.0, 0.1)
(0.0, 0.1)
(1.4, 2.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(1.3, 1.8)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.2)
(6.9, 8.1)
(0.0, 0.2)
(17.3, 19.2)(0.0, 0.1)
(0.0, 0.1)

0
1
0
0
399
0
2
1
6
1
1
23
0
5
2
22
1
0
1
1
1
2
6
5
62
6
78
0
0

0.0
0.0
0.0
0.0
4.9
0.0
0.0
0.0
0.1
0.0
0.0
0.3
0.0
0.1
0.0
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1
0.8
0.1
0.9
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(4.4, 5.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.6, 1.0)
(0.0, 0.2)
(0.8, 1.2)
(0.0, 0.0)
(0.0, 0.0)

1
1
2
2
1
0
1
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

1
0
2
7
0
1
1
0
2

0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Vaccination site swelling
Vascular stent occlusion
Vessel puncture site bruise
Vessel puncture site haematoma
Vessel puncture site induration

0
1
2
1
0

0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

1
0
0
1
1

0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

HEPATOBILIARY DISORDERS
Bile duct stone
Biliary colic
Biliary dyskinesia
Cholecystitis
Cholecystitis acute
Cholecystitis chronic
Cholelithiasis
Cirrhosis alcoholic
Gallbladder disorder
Hepatic cirrhosis
Hepatic cyst
Hepatic steatosis
Hepatocellular injury
Nonalcoholic fatty liver disease

24
2
4
1
1
4
0
11
1
1
0
1
1
0
0

0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

16
0
0
1
2
3
1
5
0
0
1
1
2
1
1

0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

IMMUNE SYSTEM DISORDERS
Allergy to animalAllergy to arthropod bite
Allergy to arthropod sting
Anaphylactic reaction
Anaphylactic shock
Drug hypersensitivity
Food allergy
Hypersensitivity
Jarisch-Herxheimer reaction
Milk allergy
Seasonal allergy

23
0
1
1
1
0
7
2
2
1
0
8

0.3
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1

(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)

34
1
1
0
0
1
7
3
5
0
1
16

0.4
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.1
0.0
0.0
0.2

(0.3, 0.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)

INFECTIONS AND INFESTATIONS
Abdominal abscess
Abscess
Abscess intestinal
Abscess jaw
Abscess limb

417
0
1
1
0
0

5.0
0.0
0.0
0.0
0.0
0.0

(4.5, 5.5)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

499
1
2
0
1
4

6.1
0.0
0.0
0.0
0.0
0.0

(5.6, 6.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Abscess neck
Abscess oral
Acarodermatitis
Acute sinusitis
Anal abscess
Anal fistula infection
Appendicitis
Appendicitis perforated
Arthritis bacterial
Bacterial blepharitis
Bacterial infection
Bacterial rhinitis
Bacterial sepsis
Bacterial vaginosis
Bacterial vulvovaginitis
Balanitis candida
Bartholin's abscess
Bartholinitis
Blister infected
Bone abscessBrain abscess
Bronchitis
COVID-19
COVID-19 pneumonia
Campylobacter infection
Carbuncle
Catheter site infection
Cellulitis
Cellulitis orbital
Chlamydial infection
Chronic sinusitis
Clostridium difficile infection
Complicated appendicitis
Conjunctivitis
Conjunctivitis bacterial
Coxsackie viral infection
Cystitis
Dental fistula
Dermatitis infected

nc

1
1
0
1
2
0
14
1
1
1
0
0
1
1
3
0
0
1
1
1
0
2
0
1
1
1
0
15
1
0
2
0
0
12
0
0
8
0
0

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)

nc

0
0
2
7
0
1
9
1
0
0
1
1
0
2
1
1
1
0
0
0
1
2
13
1
0
0
1
20
0
2
1
1
2
11
2
1
12
1
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Device related infection
Diabetic foot infection
Diverticulitis
Ear infection
Emphysematous cholecystitis
Empyema
Erysipelas
Escherichia sepsis
Escherichia urinary tract infection
Extradural abscess
Eye infection
Eye infection bacterial
Folliculitis
Fungal infection
Fungal skin infection
Furuncle
Gangrene
Gastroenteritis
Gastroenteritis viral
Gastrointestinal infection
Genital herpes
Genital herpes simplex
Genitourinary chlamydia infection
Gingival abscessGingivitis
Gonorrhoea
Groin abscessHelicobacter gastritis
Helicobacter infection
Hepatitis A
Hepatitis C
Herpes ophthalmic
Herpes simplex
Herpes virus infection
Herpes zoster
Herpes zoster cutaneous disseminated
Herpes zoster oticus
Hordeolum
Impetigo

nc

2
0
10
11
1
1
2
1
2
0
1
1
7
1
1
3
1
6
1
1
0
1
0
2
6
0
0
0
1
0
0
1
2
0
18
0
0
8
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.1
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)

nc

0
1
11
17
0
0
0
0
1
1
2
0
0
3
5
4
0
12
1
0
5
0
1
2
5
2
1
2
4
1
1
0
3
1
16
1
1
11
2

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.1
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.1
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Infected bite
Infected dermal cyst
Infectious mononucleosis
Influenza
Injection site abscess
Kidney infection
Labyrinthitis
Laryngitis
Localised infection
Lyme disease
Mastitis
Mastoiditis
Meningitis bacterial
Nail infection
Nasopharyngitis
Onychomycosis
Ophthalmic herpes zoster
Oral candidiasis
Oral fungal infection
Oral herpes
Oral infection
Orchitis
Osteomyelitis
Otitis externa
Otitis media
Otitis media acute
Otitis media bacterial
Papilloma viral infection
Parasitic gastroenteritis
Paronychia
Parotitis
Pelvic inflammatory disease
Penile infection
Periodontitis
Peritoneal abscess
Peritonitis
Peritonsillar abscessPharyngitis
Pharyngitis bacterial

nc

2
0
0
3
1
2
0
2
2
0
0
1
0
0
4
3
1
2
0
7
0
0
0
6
9
3
0
2
1
4
1
0
1
3
1
1
1
1
0

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

nc

1
2
1
1
0
1
2
0
6
2
1
0
1
1
2
3
1
1
1
7
1
2
1
7
8
2
1
0
0
2
3
1
0
3
0
1
1
3
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Pharyngitis streptococcal
Pharyngotonsillitis
Pilonidal cyst
Pneumonia
Post procedural infection
Postoperative wound infection
Primary syphilis
Pulmonary tuberculosis
Puncture site infection
PustulePyelonephritis
Pyelonephritis acute
Rash pustular
Renal abscessRespiratory tract infection viral
Rhinitis
Sepsis
Septic shock
Shigella sepsis
Sialoadenitis
Sinusitis
Sinusitis bacterial
Skin bacterial infection
Skin infection
Soft tissue infection
Staphylococcal infection
Staphylococcal sepsis
Subacute endocarditis
Subcutaneous abscess
Suspected COVID-19
Syphilis
Tinea cruris
Tinea infection
Tinea versicolour
Tonsillitis
Tonsillitis bacterial
Tooth abscess
Tooth infection
Trichomoniasis

nc

4
1
1
4
0
2
0
1
0
3
6
1
2
0
2
6
3
1
1
1
20
2
0
3
1
2
0
0
1
1
0
0
0
2
0
1
12
26
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.3
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.4)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.2, 0.5)
(0.0, 0.1)

nc

2
1
0
9
2
3
1
0
1
0
2
0
0
1
0
11
1
1
0
1
31
0
2
5
0
0
1
1
2
0
1
1
3
2
6
0
6
33
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.1
0.4
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.3, 0.5)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.2)
(0.3, 0.6)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Upper respiratory tract infection
Ureaplasma infection
Urinary tract infection
Urosepsis
Vaginal infection
Varicella
Viral infection
Viral upper respiratory tract infection
Vulval abscess
Vulvovaginal candidiasis
Vulvovaginal mycotic infection
Vulvovaginitis
Wound infection
INJURY, POISONING AND PROCEDURALCOMPLICATIONS
Administration related reaction
Alcohol poisoning
Anaemia postoperative
Animal bite
Ankle fracture
Arthropod bite
Arthropod sting
Back injury
Bone contusion
Bone fissure
Brain contusion
Burn oral cavity
Burns first degree
Burns second degree
Cartilage injury
Cervical vertebral fracture
Chest injury
Chillblains
Clavicle fracture
Colon injury
Concussion
Contusion
Corneal abrasion
Craniocerebral injury

nc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

10
0
74
0
0
1
1
0
1
4
6
1
1

0.1
0.0
0.9
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.1, 0.2)
(0.0, 0.0)
(0.7, 1.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)

9
1
82
1
7
0
1
1
0
3
10
1
0

0.1
0.0
1.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.8, 1.2)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)

294

3.5

(3.1, 3.9)

378

4.6

(4.1, 5.1)

2
1
1
3
6
12
3
0
1
1
1
1
1
3
1
3
5
0
1
0
6
14
4
2

0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.2
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)

0
0
0
7
5
7
5
2
2
1
1
0
0
0
0
1
4
1
1
1
5
22
3
4

0.0
0.0
0.0
0.1
0.1
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.3
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Delayed recovery from anaesthesia
Dental restoration failure
Ear canal abrasion
Ear injury
Epicondylitis
Exposure during pregnancy
Exposure to communicable disease
Eye contusion
Eyelid injury
Facial bones fracture
Fall
Femur fracture
Fibula fracture
Flail chest
Foot fracture
Forearm fracture
Foreign body
Foreign body aspiration
Foreign body in eye
Fractured sacrum
Hand fracture
Head injury
Heat stroke
Hip fracture
Humerus fracture
InjuryJaw fracture
Joint dislocation
Joint injury
Ligament injury
Ligament rupture
Ligament sprain
Limb fracture
Limb injury
Limb traumatic amputation
Lip injury
Lower limb fracture
Lumbar vertebral fracture
Maternal exposure before pregnancy

nc

0
0
0
1
1
30
0
0
1
5
62
0
2
0
7
0
1
0
1
1
5
4
0
2
0
0
1
8
6
0
2
21
1
8
1
1
0
1
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.1
0.7
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.3
0.0
0.1
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.6, 1.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

1
1
1
1
5
42
1
1
0
4
76
1
3
1
11
2
0
1
0
0
3
2
1
1
5
1
0
5
11
2
10
27
0
16
0
0
3
1
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.1
0.5
0.0
0.0
0.0
0.0
0.9
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.1
0.0
0.1
0.3
0.0
0.2
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.4, 0.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.7, 1.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.1, 0.2)
(0.2, 0.5)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Maternal exposure during breast feeding
Maternal exposure during pregnancy
Meniscus injury
Mouth injury
Multiple injuries
Muscle contusion
Muscle injury
Muscle rupture
Muscle strain
Overdose
Patella fracture
Pelvic fracture
Penis injury
Pharyngeal perforation
Post concussion syndrome
Post procedural discomfort
Post procedural haematoma
Post procedural haemorrhage
Post procedural swelling
Post-traumatic pain
Postoperative ileus
Procedural dizziness
Procedural haemorrhage
Procedural hypotension
Procedural pain
Radius fracture
Respiratory fume inhalation disorder
Rib fracture
Road traffic accident
Scapula fracture
Scar
Skin abrasion
Skin injury
Skin laceration
Skull fracture
Soft tissue injury
Spinal column injury
Spinal compression fracture
Spinal cord injury cervical

nc

1
4
6
0
0
1
1
1
18
4
3
2
1
0
1
1
0
0
1
0
0
0
0
1
9
2
0
3
16
1
1
8
1
18
0
0
0
2
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.2
0.0
0.0
0.1
0.0
0.2
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

0
3
10
1
1
0
3
5
17
1
1
0
0
1
0
0
1
1
0
1
1
2
1
0
5
4
1
8
20
0
0
15
1
24
1
1
1
2
0

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.2
0.0
0.0
0.2
0.0
0.3
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.1, 0.4)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Spinal fracture
Stab woundStoma site rash
Stress fracture
Subdural haematoma
Sunburn
Tendon injury
Tendon rupture
Thermal burnTibia fracture
Tooth fracture
Tooth injury
Toxicity to various agents
Traumatic haemothorax
Traumatic intracranial haemorrhage
Ulna fracture
Upper limb fracture
Vaccination complication
Venom poisoning
Vulvovaginal injury
Wound
Wrist fracture

1
1
1
1
1
1
0
0
3
3
10
0
0
0
1
1
3
5
0
0
2
3

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

1
0
0
5
1
0
2
6
4
1
10
1
1
1
0
2
2
0
1
1
5
5

0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

INVESTIGATIONS
Alanine aminotransferase increased
Aspartate aminotransferase increased
Autoantibody positive
Biopsy breast normal
Blood chloride decreased
Blood cholesterol increased
Blood creatinine decreased
Blood creatinine increased
Blood glucose abnormal
Blood glucose fluctuation
Blood glucose increased
Blood immunoglobulin E increased
Blood iron decreased
Blood potassium decreased
Blood pressure abnormal

183
2
1
0
0
0
5
1
0
1
1
8
1
0
2
0

2.2
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(1.9, 2.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

51
0
0
1
1
1
2
0
1
1
0
1
0
1
0
1

0.6
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.5, 0.8)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Blood pressure diastolic increased
Blood pressure increased
Blood pressure systolic increased
Blood sodium decreased
Blood testosterone decreased
Blood testosterone increased
Blood thyroid stimulating hormone increased
Blood triglycerides increased
Blood urea increased
Body temperature
Body temperature decreased
Body temperature increased
C-reactive protein
Cardiac stress test abnormal
Electrocardiogram QT prolonged
Fractional exhaled nitric oxide increased
Glomerular filtration rate decreased
Haemoglobin decreased
Heart rate increased
Heart rate irregularHepatic enzyme increased
Hepatitis C antibody positive
Herpes simplex test positive
High density lipoprotein increased
Intraocular pressure increased
Liver function test increased
Low density lipoprotein increased
Lymphocyte count decreased
Mammogram abnormal
Mean cell haemoglobin decreased
Mean cell volume decreased
Mean cell volume increased
Monocyte count increased
Platelet count decreased
Platelet count increased
Prostatic specific antigen increased
Red blood cell morphology abnormal
Respiratory rate increased
SARS-CoV-2 antibody test positive

nc

0
6
1
0
1
1
3
1
0
1
1
121
1
1
1
1
1
1
4
0
0
0
1
0
0
1
4
1
2
0
1
0
0
1
1
1
0
1
4

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
1.5
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(1.2, 1.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

1
10
0
1
0
0
1
0
1
0
0
13
0
0
0
0
0
0
2
1
2
1
0
2
1
0
1
0
0
1
0
1
1
0
0
2
1
0
0

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Serum ferritin decreased
Thyroid function test abnormal
Troponin increased
Urine ketone body present
Weight decreased
Weight increased
White blood cell count increased
White blood cells urine positive

0
0
2
0
3
2
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
1
0
1
0
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

METABOLISM AND NUTRITIONDISORDERS
Decreased appetite
Dehydration
Diabetes mellitus
Diabetes mellitus inadequate control
Diabetic ketoacidosis
Dyslipidaemia
Fluid retention
Folate deficiency
Food intolerance
Glucose tolerance impaired
Gout
Hypercholesterolaemia
Hyperglycaemia
Hyperkalaemia
Hyperlipidaemia
Hypernatraemia
Hypertriglyceridaemia
Hyperuricaemia
Hypocalcaemia
Hypocholesterolaemia
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypovolaemia
Impaired fasting glucose
Increased appetite
Insulin resistanceIron deficiency

129

1.5

(1.3, 1.8)

117

1.4

(1.2, 1.7)

39
3
2
1
1
7
1
1
1
3
5
7
2
2
9
1
2
2
1
1
3
8
1
1
0
1
0
2
1

0.5
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.3, 0.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

9
5
1
3
1
8
0
0
0
5
3
21
6
0
11
0
0
1
1
1
3
8
0
1
1
0
1
2
2

0.1
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.3
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.2)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Lactic acidosis
Obesity
Polydipsia
Type 2 diabetes mellitus
Vitamin B12 deficiency
Vitamin D deficiency
MUSCULOSKELETAL AND CONNECTIVE
TISSUE DISORDERS
Arthralgia
Arthritis
Arthritis reactive
Arthropathy
Axillary mass
Back pain
Bone disorder
Bone pain
Bone swelling
Bursitis
Coccydynia
Costochondritis
Dupuytren's contracture
Exostosis
Fibromyalgia
Flank pain
Groin pain
Intervertebral disc compression
Intervertebral disc degeneration
Intervertebral disc disorderIntervertebral disc protrusion
Joint effusion
Joint instability
Joint range of motion decreased
Joint stiffness
Joint swelling
Limb discomfort
Metatarsalgia
Mobility decreased
Muscle contracture
Muscle discomfort

nc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
2
2
14
1
12

0.0
0.0
0.0
0.2
0.0
0.1

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.1, 0.3)

1
0
0
13
5
10

0.0
0.0
0.0
0.2
0.1
0.1

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.1, 0.2)

1859

22.3

(21.3, 23.3)

622

7.6

(7.0, 8.2)

281
6
1
2
1
104
1
3
0
11
2
5
0
5
1
3
1
1
4
0
10
2
1
5
5
2
3
0
2
4
0

3.4
0.1
0.0
0.0
0.0
1.2
0.0
0.0
0.0
0.1
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.0

(3.0, 3.8)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(1.0, 1.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

122
6
0
1
1
99
0
0
1
5
1
0
1
3
3
4
1
0
5
1
11
0
0
0
1
5
1
2
0
8
1

1.5
0.1
0.0
0.0
0.0
1.2
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0

(1.2, 1.8)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(1.0, 1.5)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Muscle fatigue
Muscle spasms
Muscle tightness
Muscle twitching
Muscular weakness
Musculoskeletal chest pain
Musculoskeletal discomfort
Musculoskeletal pain
Musculoskeletal stiffness
Myalgia
Myalgia intercostal
Neck pain
Osteitis
Osteoarthritis
Osteochondritis
Osteochondrosis
Osteopenia
Osteoporosis
Pain in extremity
Pain in jaw
Patellofemoral pain syndrome
Periarthritis
Plantar fasciitis
Polyarthritis
Psoriatic arthropathy
Rhabdomyolysis
Rheumatoid arthritis
Rotator cuff syndrome
Scoliosis
Sinus tarsi syndrome
Spinal disorder
Spinal osteoarthritis
Spinal stenosis
Spondylitis
Spondylolisthesis
Synovial cyst
Synovitis
Systemic lupus erythematosus
Temporomandibular joint syndrome

nc

4
29
1
3
13
11
4
2
12
1245
0
34
1
15
1
0
1
0
189
3
0
4
4
0
2
1
0
5
0
0
0
2
1
1
1
3
0
1
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.3
0.0
0.0
0.2
0.1
0.0
0.0
0.1
14.9
0.0
0.4
0.0
0.2
0.0
0.0
0.0
0.0
2.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(14.1, 15.8)(0.0, 0.0)
(0.3, 0.6)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(2.0, 2.6)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

1
16
0
2
3
7
2
4
6
170
1
36
1
23
0
1
4
6
52
3
1
1
8
1
2
1
2
13
2
1
1
4
1
1
1
2
2
0
4

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.2
0.0
0.0
0.0
0.1
0.0
0.0
0.1
2.1
0.0
0.4
0.0
0.3
0.0
0.0
0.0
0.1
0.6
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(1.8, 2.4)
(0.0, 0.1)
(0.3, 0.6)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.5, 0.8)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Tendon disorder
Tendon pain
Tendonitis
Tenosynovitis
Tenosynovitis stenosans
Torticollis
Trigger finger
NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS)
Acrochordon
Acute myeloid leukaemia
Adenocarcinoma gastric
Adenocarcinoma of colon
Adenocarcinoma pancreas
Adenoma benign
Adrenal gland cancer
B-cell lymphoma
Basal cell carcinoma
Benign breast neoplasm
Benign hydatidiform mole
Benign pancreatic neoplasm
Benign uterine neoplasm
Biliary cancer metastatic
Bladder cancer
Borderline serous tumour of ovary
Breast cancer
Breast cancer in situ
Breast cancer stage I
Carcinoid tumour of the stomach
Chondroma
Chronic myeloid leukaemia
Clear cell renal cell carcinoma
Colon adenoma
Fibroadenoma of breast
Gallbladder cancer stage II
Gastric cancer
Glomus tumour
Haemangioma of skin
Infected naevus

nc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

3
1
12
0
2
1
2

0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
0
10
1
3
2
4

0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

67

0.8

(0.6, 1.0)

69

0.8

(0.7, 1.1)

0
1
1
1
2
1
1
0
3
1
1
1
1
0
1
1
2
1
0
1
1
0
0
3
0
1
1
0
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2
0
0
0
0
0
0
1
11
0
0
0
0
1
1
0
7
0
1
0
0
1
1
2
2
0
0
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Intraductal proliferative breast lesion
Invasive ductal breast carcinoma
Leydig cell tumour of the testis
LipomaLobular breast carcinoma in situ
Lung adenocarcinoma
Lung cancer metastatic
Lymphoma
Lymphoproliferative disorder
Malignant melanoma
Malignant melanoma of eyelid
Meningioma
Meningioma benign
Metastases to central nervous system
Metastases to liver
Metastases to lymph nodes
Non-Hodgkin's lymphoma recurrent
Non-small cell lung cancer stage IV
Oropharyngeal cancer recurrent
Oropharyngeal squamous cell carcinoma
Ovarian germ cell teratoma benign
Pancreatic carcinoma
Papillary serous endometrial carcinoma
Papillary thyroid cancer
Penile neoplasm
Penile squamous cell carcinoma
Plasma cell myeloma
Polycythaemia vera
Prostate cancer
Prostate cancer metastatic
Seborrhoeic keratosis
Skin cancer
Skin papilloma
Squamous cell carcinoma
Squamous cell carcinoma of head and neck
Squamous cell carcinoma of skin
Teratoma
Thyroid cancer
Tonsil cancer

nc

0
2
1
5
0
0
1
1
1
3
1
1
1
1
0
0
0
1
0
1
1
0
0
0
1
1
1
0
5
1
1
1
1
1
0
1
0
1
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

2
2
0
7
1
2
0
0
0
6
0
0
0
0
1
2
1
0
1
0
0
1
1
1
0
0
0
1
2
0
0
0
0
1
1
2
1
0
0

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Transitional cell carcinoma
Uterine cancer
Uterine leiomyoma
NERVOUS SYSTEM DISORDERS
Ageusia
Amnesia
Amyotrophic lateral sclerosis
Aphasia
Balance disorder
Burning sensation
Carpal tunnel syndrome
Cerebellar infarction
Cerebral atrophy
Cerebral capillary telangiectasia
Cerebral infarction
Cerebrovascular accident
Cervical radiculopathy
Cervicogenic headache
Dementia Alzheimer's type
Depressed level of consciousness
Diabetic neuropathy
Disturbance in attention
Dizziness
Dizziness postural
Drug withdrawal headache
Dysgeusia
Dyskinesia
Dystonia
Facial paralysis
Facial paresis
Generalised tonic-clonic seizure
Guillain-Barre syndrome
Haemorrhagic stroke
Head discomfort
HeadacheHemiparaesthesia
Hemiplegic migraine
Hyperaesthesianc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

3
0
2

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

0
1
4

0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

1602
0
1
0
2
1
3
2
0
0
0
0
4
2
0
0
1
1
4
81
2
1
12
1
0
4
0
0
0
0
1
1348
0
0
4

19.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
1.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
16.2
0.0
0.0
0.0

(18.3, 20.2)(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.8, 1.2)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(15.3, 17.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

635
1
1
1
1
0
3
6
1
1
1
1
1
2
1
1
0
1
0
64
1
0
8
0
1
1
1
1
1
1
2
429
1
1
0

7.7
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.8
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
5.2
0.0
0.0
0.0

(7.1, 8.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.6, 1.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(4.7, 5.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Hypersomnia
Hypoaesthesia
Hypogeusia
Hyposmia
Idiopathic intracranial hypertension
Intraventricular haemorrhage
Ischaemic stroke
Lethargy
Mental impairment
Migraine
Migraine with aura
Migraine without aura
Morton's neuralgia
Motor dysfunction
Muscle spasticity
Myoclonus
Nerve compression
Neuralgia
Neuritis
Neuropathy peripheral
Nystagmus
Optic neuritis
Paraesthesia
Paraparesis
Parkinsonism
Parosmia
Periodic limb movement disorder
Peripheral nerve lesion
Peripheral sensory neuropathy
Piriformis syndrome
Post herpetic neuralgia
Presyncope
Radiculopathy
Restless legs syndrome
Sciatic nerve neuropathy
Sciatica
SeizureSinus headache
Somnolence

nc

1
5
0
0
2
0
2
25
1
26
1
3
0
1
0
0
3
1
0
1
0
2
23
0
0
5
1
1
1
1
2
8
2
3
0
13
2
3
9

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.2
0.0
0.0
0.1

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)

nc

1
8
1
1
0
1
2
6
1
13
1
0
1
0
1
1
2
1
1
3
1
0
24
1
1
1
0
0
0
0
0
5
1
0
1
11
1
1
11

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.1

(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Spinal cord compression
Subarachnoid haemorrhage
Syncope
Taste disorder
Tension headache
Thoracic radiculopathy
Toxic encephalopathy
Transient global amnesia
Transient ischaemic attack
TremorTrigeminal neuralgia
Uraemic encephalopathy
VIth nerve paralysisnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
4
14
2
11
0
1
1
2
9
0
1
0

0.0
0.0
0.2
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

1
1
13
0
9
1
0
0
3
6
2
0
1

0.0
0.0
0.2
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

PREGNANCY, PUERPERIUM AND
PERINATAL CONDITIONS
Abortion incomplete
Abortion spontaneous
Abortion spontaneous incomplete
Retained products of conception

2

0.0(0.0, 0.1)

6

0.1

(0.0, 0.2)

0
2
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
3
1
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

PRODUCT ISSUES
Device breakage
Device connection issue

1
0
1

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

1
1
0

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

PSYCHIATRIC DISORDERS
Abnormal dreams
Adjustment disorder with depressed mood
Alcohol abuse
Alcohol withdrawal syndrome
Anxiety
Anxiety disorder
Attention deficit hyperactivity disorder
Bipolar disorder
Bruxism
Confusional state
Cyclothymic disorder
Depressed mood
Depression
Depression suicidal
Disorientation

112
3
0
0
1
27
4
5
0
1
0
0
1
23
0
5

1.3
0.0
0.0
0.0
0.0
0.3
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.1

(1.1, 1.6)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)

108
0
1
1
1
31
4
8
3
1
1
1
2
26
1
0

1.3
0.0
0.0
0.0
0.0
0.4
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0

(1.1, 1.6)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.3, 0.5)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Dysphemia
Gastrointestinal somatic symptom disorder
Generalised anxiety disorder
Insomnia
Irritability
Libido decreased
Libido increased
Listless
Major depression
Mental disorder
Mental fatigue
Mental status changes
Mood swings
Nightmare
Panic attack
Panic disorder
Panic reaction
Paranoia
Post-traumatic stress disorder
Psychotic disorder
Restlessness
Schizophrenia
Sleep disorder
StressSubstance abuse
Suicidal ideation
Suicide attempt
RENAL AND URINARY DISORDERS
Acute kidney injury
Bladder spasm
Chronic kidney disease
Costovertebral angle tenderness
Dysuria
Haematuria
Hydronephrosis
Hypertonic bladder
Micturition urgency
Nephrolithiasis

nc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
0
1
25
4
1
1
1
0
2
0
2
0
2
2
0
0
1
1
1
1
1
4
0
1
0
1

0.0
0.0
0.0
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

1
1
3
13
2
0
0
0
1
0
1
0
1
0
5
1
1
0
0
0
0
0
0
1
0
3
1

0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

52
6
2
1
0
8
5
1
1
1
14

0.6
0.1
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.2

(0.5, 0.8)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)

48
5
0
2
1
5
7
2
1
0
15

0.6
0.1
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.2

(0.4, 0.8)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Nocturia
Obstructive nephropathy
Oedematous kidney
Perinephric oedema
Pollakiuria
Polyuria
Renal atrophy
Renal colic
Renal cyst
Renal cyst haemorrhage
Renal failure
Subcapsular renal haematoma
Ureterolithiasis
Urethral discharge
Urethral stenosis
Urinary bladder polyp
Urinary retention
Urinary tract obstruction
Urine odour abnormal
Vesical fistula
REPRODUCTIVE SYSTEM AND BREASTDISORDERS
Adenomyosis
Adnexal torsion
Amenorrhoea
Benign prostatic hyperplasia
Breast calcifications
Breast cyst
Breast hyperplasia
Breast mass
Breast pain
Cervical dysplasia
Cervical polypDysfunctional uterine bleeding
Dysmenorrhoea
Ejaculation disorder
Endometriosis
Erectile dysfunction
Genital erythemanc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
1
0
0
5
0
0
2
1
0
0
1
1
0
1
0
2
1
0
1

0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

1
0
1
1
4
1
1
2
0
1
1
0
0
1
0
1
2
0
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

50

0.6

(0.4, 0.8)

58

0.7

(0.5, 0.9)

0
0
2
3
0
0
1
1
4
1
1
1
4
0
1
1
2

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

1
2
3
3
1
3
2
2
0
0
0
0
3
1
1
6
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Haematospermia
Haemorrhagic ovarian cyst
Mammary duct ectasia
Menometrorrhagia
Menorrhagia
Menstruation delayed
Menstruation irregular
Metrorrhagia
Nipple pain
Ovarian cyst
Ovarian mass
Pelvic pain
Penile vein thrombosis
Polycystic ovaries
Postmenopausal haemorrhage
Premenstrual syndrome
Prostatitis
Prostatomegaly
Pruritus genital
Rectocele
Scrotal pain
Testicular pain
Testicular torsion
Uterine haemorrhage
Uterine inflammation
Uterine prolapse
Vaginal discharge
Vaginal haemorrhage
Vaginal prolapse
Vulvovaginal pruritus

1
1
1
1
1
0
2
2
0
5
0
3
0
1
1
0
1
2
1
0
1
2
1
0
0
1
0
1
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

0
1
0
0
2
2
0
2
1
1
1
3
1
0
1
1
3
1
1
1
0
1
0
2
1
0
1
3
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

RESPIRATORY, THORACIC AND
MEDIASTINAL DISORDERS
Acute respiratory failure
Allergic respiratory disease
Allergic sinusitis
AsthmaAsthma exercise induced
Asthmatic crisis
Atelectasis

224

2.7

(2.3, 3.1)

195

2.4

(2.1, 2.7)

2
0
2
15
1
2
1

0.0
0.0
0.0
0.2
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

3
1
0
9
2
1
0

0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Bronchospasm
Chronic obstructive pulmonary disease
Cough
Dry throat
Dysphonia
Dyspnoea
Dyspnoea exertional
Emphysema
Epistaxis
Haemoptysis
Hiccups
HypoxiaInterstitial lung disease
Lung infiltration
Nasal congestion
Nasal discomfort
Nasal obstruction
Nasal polyps
Nasal septum deviation
Nasal turbinate hypertrophy
Nasal valve collapse
Nasopharyngeal polyp
Oropharyngeal discomfort
Oropharyngeal pain
Paranasal sinus discomfort
Paranasal sinus hypersecretion
Pharyngeal lesion
Pharyngeal swelling
Pleurisy
Pleuritic pain
Pneumonia aspiration
Pneumonitis
Pneumothorax
Productive coughPulmonary embolism
Pulmonary hypertension
Pulmonary mass
Pulmonary oedema
Pulmonary pain

nc

3
6
23
3
2
6
1
1
6
1
1
0
1
0
30
1
1
2
2
0
0
0
2
36
4
1
0
1
1
0
1
1
1
2
8
1
0
0
0

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.1
0.3
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.2)
(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.3, 0.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

nc

3
1
15
0
4
11
3
0
9
1
0
1
2
1
33
0
0
1
1
1
1
1
3
31
6
0
1
3
0
1
1
0
1
2
8
0
3
1
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.2
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.4
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.3, 0.6)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.3, 0.5)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Reflux laryngitis
Respiratory arrest
Respiratory failure
Respiratory tract congestion
Rhinalgia
Rhinitis allergic
Rhinitis perennial
Rhinorrhoea
Sinus congestion
Sinus disorder
Sleep apnoea syndrome
Sneezing
Snoring
Sputum discoloured
Throat irritation
Tonsillar hypertrophy
Upper respiratory tract congestion
Upper-airway cough syndrome
Wheezing
SKIN AND SUBCUTANEOUS TISSUEDISORDERS
Acne
Acne cystic
Actinic keratosis
Alopecia
Alopecia areata
Angioedema
Blister
Cold sweat
Dermal cyst
Dermatitis
Dermatitis acneiform
Dermatitis allergic
Dermatitis atopic
Dermatitis bullous
Dermatitis contact
Dermatitis exfoliative
Diabetic footDrug eruptionnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
0
1
2
0
13
0
21
6
0
6
3
1
0
7
1
4
8
3

0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.3
0.1
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.0)
(0.2, 0.4)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)

1
1
1
2
1
14
1
13
7
1
2
3
1
1
9
0
1
6
1

0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.2
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)

254

3.0

(2.7, 3.4)

194

2.4

(2.0, 2.7)

4
1
3
5
1
3
1
2
5
5
1
3
0
0
14
1
2
0

0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

3
1
3
6
1
2
2
0
1
4
0
5
1
1
21
0
1
2

0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.3
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Dry skin
Dyshidrotic eczema
Ecchymosis
EczemaErythema
Erythema nodosum
Fixed eruption
Hand dermatitis
Hangnail
Hidradenitis
Hyperhidrosis
Ingrowing nailIntertrigo
Lipodystrophy acquired
Livedo reticularis
MaculeMechanical urticaria
Night sweats
Onycholysis
Onychomadesis
Pain of skin
PapulePeau d'orange
Perioral dermatitis
Pityriasis
Pityriasis rosea
Pruritus
Pruritus allergic
Pseudofolliculitis
Psoriasis
PurpuraRash
Rash erythematous
Rash maculo-papular
Rash papular
Rash pruritic
Rosacea
Seborrhoeic dermatitis
Skin discolouration

nc

1
0
1
7
9
1
1
2
1
1
31
0
1
0
1
1
0
17
1
1
1
3
0
0
1
1
24
0
1
1
1
62
2
7
2
8
1
0
1

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.0
0.0
0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.3
0.0
0.0
0.0
0.0
0.7
0.0
0.1
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.3, 0.5)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.6, 1.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

nc

0
1
2
3
2
0
0
2
0
0
9
2
0
1
0
1
1
3
0
0
1
0
1
1
0
3
20
2
0
2
0
52
3
4
1
6
1
3
0

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.6
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.4)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.5, 0.8)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

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BNT162b2
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Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Skin induration
Skin irritation
Skin lesion
Skin mass
Skin ulcer
Stasis dermatitis
Transient acantholytic dermatosis
Urticaria
Urticaria contact
Urticaria papularnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
1
3
1
1
0
1
18
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.0)

1
0
8
1
0
1
0
15
1
1

0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)

SOCIAL CIRCUMSTANCESHigh risk sexual behaviour
Menopause
Miscarriage of partner

5
2
2
1

0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
0
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SURGICAL AND MEDICAL PROCEDURES
Abortion induced
Apicectomy
Botulinum toxin injection
Cardiac pacemaker replacement
Cardioversion
Carpal tunnel decompression
Cataract operation
Chondroplasty
Dental care
Dental implantation
Drug titration
Endodontic procedure
Facet joint block
Finger amputation
Gingival operation
Inguinal hernia repair
Lacrimal duct procedure
Lens extraction
Mammoplasty
Medical device implantation
Nasal polypectomy
Open reduction of fracture
Postoperative care

33
0
1
1
1
1
1
0
0
0
5
1
2
1
1
1
1
1
0
1
0
0
1
1

0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.3, 0.6)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

26
1
0
0
0
0
0
1
1
2
3
0
1
0
0
0
0
0
1
0
1
1
0
0

0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.2, 0.5)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Retinal operation
Rhinoplasty
Rotator cuff repair
Sclerotherapy
Skin neoplasm excision
Toe amputation
Toe operation
Tonsillectomy
Tooth extraction
Vasectomy
Wisdom teeth removal
Wound drainage
VASCULAR DISORDERS
Accelerated hypertension
Aortic aneurysm
Aortic dilatation
Aortic rupture
Aortic stenosis
Arteriosclerosis
Blood pressure inadequately controlled
Deep vein thrombosis
Diastolic hypertension
Essential hypertension
Flushing
Haematoma
Hot flush
Hypertension
Hypertensive crisis
Hypertensive emergency
Hypertensive urgency
Hypotension
Intermittent claudication
Lymphoedema
Lymphorrhoea
Orthostatic hypotension
Pallor
Peripheral arterial occlusive disease
Peripheral artery stenosisnc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
0
1
1
1
0
0
0
6
0
2
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

0
1
0
0
0
1
2
1
6
1
2
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

112
0
1
1
0
0
2
0
7
0
1
11
4
7
61
1
0
3
6
1
0
1
1
0
0
0

1.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.1
0.7
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(1.1, 1.6)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.2)
(0.6, 0.9)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

118
2
3
0
1
2
2
1
7
1
0
2
4
9
68
1
1
1
3
0
1
0
4
1
1
1

1.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.8
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(1.2, 1.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.6, 1.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 8.

Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding
Date, by System Organ Class and Preferred Term – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Phlebitis superficial
Phlebolith
Raynaud's phenomenon
Subgaleal haematoma
Systolic hypertension
Thrombophlebitis superficial
Varicose vein
Venous thrombosis limb

nc

0
0
0
0
1
1
2
0

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

nc

1
1
1
1
0
0
1
1

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:11)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 all exp p3 saf

Subgroup Analyses
In the baseline SARS-CoV-2 positive subgroup, differences in IRs in the BNT162b2(70.7 per 100 PY) and placebo (31.9 per 100 PY) groups were due to reactogenicity events(chills, fatigue, injection site pain, pyrexia, myalgia, and headache).
In the baseline SARS-CoV-2 negative subgroup, differences in IRs in the BNT162b2(83.6 per 100 PY) and placebo (43.8 per 100 PY) groups were due to reactogenicity events(diarrhea, vomiting, chill, fatigue, injection site reactions [pain, erythema, swelling], pyrexia,
arthralgia, myalgia, and headache) as well as other AEs (lymphadenopathy, nausea, asthenia,
malaise, pain, body temperature increase, and pain in extremity).
Given the differences in exposure (2.5 vs 80.4) by baseline SARS-CoV-2 positive andnegative status, respectively, direct comparisons should be interpreted with caution. The
overall rate of AEs is 70.7 per 100 PY (95% CI: 60.7, 81.9) (baseline positive) comparedwith 83.6 per 100 PY (95% CI: 81.7, 85.7) (baseline negative). For other SOCs, the IR were
either numerically lower or similar for the baseline positive group compared to the baseline
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BNT162b2
2.7.4 Summary of Clinical Safety

negative group. Overall, there is no evidence that individuals who are positive at baseline
report AEs at a higher frequency than those who are negative at baseline.
In the BNT162b2 group, overall IRs for participants reporting at least 1 AE were highest forparticipants of all other races (120.1 per 100 PY) compared to White participants (83.1 per
100 PY), with Black or African American participants having the lowest IR (53.5 per 100
PY). The IR for nausea in the BNT162b2 group was higher in participants of all other races(4.7 per 100 PY BNT162b2 vs 1.6 per 100 PY placebo) and White participants (3.4 per 100
PY BNT162b2 vs 1.0 per 100 PY placebo) than in Black or African American participants
where the IR was similar in both vaccine groups (1.3 per 100 PY BNT162b2 vs 1.2 per 100
PY placebo).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

In the BNT162b2 group, the IR for participants reporting at least 1 AE was higher in nonHispanic/non-Latino participants (85.4 per 100 PY BNT162b2 and 41.6 per 100 PY placebo)and Hispanic/Latino participants (78.4 per 100 PY BNT162b2 and 47.9 per 100 PY placebo)and lowest in the group where ethnicity was not reported (49.4 per 100 PY BNT162b2 and43.3 per 100 PY placebo). IRs were higher for mainly reactogenicity events (chills, fatigue,
myalgia, diarrhea, injection site reactions [pain, erythema, and swelling], pain, pyrexia, andheadache) as well as lymphadenopathy, nausea, influenza like illness, malaise, increased
body temperature, and pain in extremity.
Overall, females reported a higher IR of AEs (91.0 per 100 PY BNT162b2, 46.8 per 100 PY
placebo) than males (76.0 per 100 PY BNT162b2, 40.1 per 100 PY placebo), with a greater
difference in the BNT162b2 groups than in the placebo groups . The higher IRs in females
were due to reactogenicity AEs (vomiting, chills, fatigue, pyrexia, myalgia, and headache) as
well as other AEs (lymphadenopathy, nausea, pain, increased body temperature, and pain in
extremity). There were sex appropriate differences as well, such as higher IRs in the SOC ofcardiac disorders in males (1.2 per 100 PY) versus females (0.9 per 100 PY) and lower IRs in
the SOC of reproductive system and breast disorders in males (0.3 per 100 PY) versus
females (0.9 per 100 PY).
2.7.4.2.4.2.2.2.1.1. Participants with Confirmed Stable HIV Disease: Blinded PlaceboControlled Follow-Up Period From Dose 1 to the Unblinding Date (Phase 3, Study
C4591001, Analysis of Adverse Events, Adverse Events by System Organ Class andPreferred Term)
From Dose 1 to the unblinding date, and similar to the overall population, most AEs reported
for the subset of 200 HIV-positive participants from Dose 1 to the unblinding date were in
SOCs with reactogenicity events:

general disorders and administration site conditions (66.1 per 100 PY BNT162b2 vs
6.9 per 100 PY placebo)
musculoskeletal and connective tissue disorders (19.8 per 100 PY BNT162b2 vs 10.4
per 100 PY placebo)
nervous system disorders (16.5 per 100 PY BNT162b2 vs 0.0 placebo per 100 PY)
gastrointestinal disorders (9.9 per 100 PY BNT162b2 vs 13.9 placebo)

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2.7.4.2.4.2.2.2.2. Related Adverse Events by System Organ Class and Preferred Term:
Blinded Placebo-Controlled Follow-Up Period From Dose 1 to the Unblinding Date
(Phase 3, Study C4591001)
From Dose 1 to the unblinding date, IRs of AEs assessed as related by the investigator during
the blinded follow-up period were 62.9 per 100 PY and 16.0 per 100 PY in the BNT162b2
group and in the placebo group, respectively (Table 7). The IRs of related AEs were highest
for reactogenicity events and in the SOC of general disorders and administration site
conditions, IRs were 55.7 per 100 PY and 10.8 per 100 PY for BNT162b2 and placebo
recipients, respectively. Additional terms identified as either synonymous with or otherwise
plausibly associated with reactogenicity events (ie, secondary to reactogenicity events)
occurring within 7 days after each dose were also considered related (pain in extremity,
decreased appetite, lethargy, asthenia, malaise, night sweats, and hyperhidrosis)(Section 2.7.4.2.4.2.1.2.1).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Lymphadenopathy is discussed in Section 2.7.4.2.4.3.4.1.3. IRs of related AEs in the younger
and older age groups were 70.0 per 100 PY and 52.3 per 100 PY, respectively for the
BNT162b2 group and 18.0 per 100 PY and 13.0 per 100 PY, respectively, for the placebogroup.
2.7.4.2.4.2.2.2.3. Severe or Life-Threatening Adverse Events: Blinded PlaceboControlled Follow-Up Period From Dose 1 to the Unblinding Date (Phase 3, Study
C4591001)
From Dose 1 to the unblinding date, severe AE IRs during the blinded follow-up period were
4.3 per 100 PY (95% CI: 3.8, 4.7) and 3.1 per 100 PY (95% CI: 2.7, 3.5) in BNT162b2 andplacebo recipients, respectively. Severe events in the general disorders and administrationsite conditions were generally reflecting terms consistent with reactogenicity, in the
BNT162b2 versus placebo groups (1.2 per 100 PY vs 0.1 per 100 PY) as well as the
Musculoskeletal SOC (0.6 per 100 PY vs 0.3 per 100 PY). The IR in all other SOCs weresimilar in the BNT162b2 and placebo groups.
The IRs for participants who had at least 1 life-threatening AE from Dose 1 to the unblinding
date were similar: 0.6 per 100 PY (95% CI: 0.4, 0.8) in the BNT162b2 group and 0.7 per 100
PY (95% CI: 0.5, 0.9) in the placebo group. All of the IRs for the SOCs were similar in the
BNT162b2 and placebo groups.
2.7.4.2.4.2.3. Open-Label Follow-Up Period – Original BNT162b2 Participants (Phase
3, Study C4591001)
2.7.4.2.4.2.3.1. Summary of Adverse Events: Open-Label Follow-Up Period – Original
BNT162b2 Participants (Phase 3, Study C4591001)
Per protocol AEs are reported through 1 month after the Dose 2 and within 48 hours after ablood draw. SAEs are reported to approximately 6 months after the last dose of study
intervention. An overview of IRs of AEs from the unblinding date to the data cutoff date forparticipants originally randomized to BNT162b2 during the open-label follow-up ispresented in Table 9. The IRs for any AE, at least 1 related AE, and severe AE were 8.8 per
100 PY, and 0.7 per 100 PY, and 1.6 per 100 PY, respectively, which is markedly reduced
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relative to those from Dose 1 to the unblinding date (83.2, 62.9, 4.3 respectively [Table 7] ).
The IR of life-threatening AEs is 0.4 per 100 PY (95% CI: 0.2, 0.8), which is similar to the
IR from Dose 1 to the unblinding date, 0.6 per 100 PY (95% CI: 0.4, 0.8).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The IR of SAEs during the open-label follow-up period (Table 9), 2.0 per 100 PY (95% CI:
1.5, 2.6) were lower than the IR from Dose 1 to the unblinding date, 3.2 per 100 PY (95% CI:
2.8, 3.6) (Table 7). There was a single related SAE (myocardial infarction) for an individualin the open label follow-up period (see Section 2.7.4.2.4.3.2.3). The IR of AEs leading towithdrawal also decreased (0.1 per 100 PY [95% CI: 0.0, 0.4]) in the open-label follow-up
period compared with the blinded placebo-controlled period (0.5 per 100 PY [95% CI: 0.4,0.7]) but the IR of deaths were similar (0.1 per 100 PY vs 0.2 per 100 PY in the open-label
and blinded placebo-controlled follow-up periods, respectively).

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Table 9.

Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021) – Open-Label Follow-up Period – Subjects
Who Originally Received BNT162b2 – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)

Adverse Eventnc

Any event
Relatedf
SevereLife-threatening
Any serious adverse event
Relatedf
SevereLife-threatening
Any adverse event leading to withdrawal
Relatedf
SevereLife-threatening
Death

243
20
43
12
55
1
30
12
4
0
0
4
3

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)
8.8
0.7
1.6
0.4
2.0
0.0
1.1
0.4
0.1
0.0
0.0
0.1
0.1

(7.7, 9.9)
(0.4, 1.1)
(1.1, 2.1)
(0.2, 0.8)
(1.5, 2.6)
(0.0, 0.2)
(0.7, 1.5)
(0.2, 0.8)
(0.0, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.4)
(0.0, 0.3)

a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from the unblinding date to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number ofsubjects reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s092_unb_cut_p3_saf

2.7.4.2.4.2.3.2. Analysis of Adverse Events: Open-Label Follow-Up Period – Original
BNT162b2 Participants ≥16 Years of Age (Phase 3, Study C4591001)
2.7.4.2.4.2.3.2.1. Adverse Events by System Organ Class and Preferred Term: OpenLabel Follow-Up Period – Original BNT162b2 Participants ≥16 Years of Age (Phase 3,
Study C4591001, Analysis of Adverse Events)
From the unblinding date to the data cutoff date for participants originally randomized to
BNT162b2 during the open-label follow-up period, the IR for participants who reported at
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least 1 AE was 8.8 per 100 PY compared to 83.2 per 100 PY from Dose 1 to the unblinding
date (Table 7).
Overall, the rates in all SOCs after the unblinding date decreased or remained similar to thosein the blinded placebo-controlled period.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The IR for the SOC of injury, poisoning and procedural complications was 1.4 per 100 PY,
with the PT fall having the highest IR (0.4 per 100 PY). The IR for the SOC of vasculardisorders was 0.8 per 100 PY, with the PT hypertension having the highest IR (0.6 per
100 PY).

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Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event

243

8.8

(7.7, 9.9)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymph node pain
Lymphadenopathy
Pancytopenia
Splenic infarction
Splenomegaly

5
1
3
1
1
1

0.2
0.0
0.1
0.0
0.0
0.0

(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

CARDIAC DISORDERS
Atrial fibrillation
Atrial flutter
Cardiac failure congestive
CardiomegalyCoronary artery disease
Coronary artery occlusion
Myocardial infarction
Tachycardia

14
2
1
1
1
3
1
4
1

0.5
0.1
0.0
0.0
0.0
0.1
0.0
0.1
0.0

(0.3, 0.8)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Benign familial pemphigus

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

EAR AND LABYRINTH DISORDERS
Vertigo

2
2

0.1
0.1

(0.0, 0.3)
(0.0, 0.3)

ENDOCRINE DISORDERS
Hyperthyroidism
Pituitary cyst

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

EYE DISORDERS
Blepharitis
Dry eyeGlaucoma
Macular oedema
Retinal tear

6
1
1
2
1
1

0.2
0.0
0.0
0.1
0.0
0.0

(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

GASTROINTESTINAL DISORDERS
Abdominal pain upper
Diverticulum
Dyspepsia
Eosinophilic oesophagitis

17
1
1
1
1

0.6
0.0
0.0
0.0
0.0

(0.4, 1.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Gastritis
Gastritis alcoholic
Gastritis erosive
Gastrointestinal haemorrhage
Gastrooesophageal reflux disease
Haematemesis
Hiatus hernia
Irritable bowel syndrome
Pancreatic calcification
Rectal haemorrhage

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

1
1
1
1
3
1
2
2
1
2

0.0
0.0
0.0
0.0
0.1
0.0
0.1
0.1
0.0
0.1

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONSChest pain
ChillsFatigue
Impaired healing
Injection site pain
Injection site swelling
Non-cardiac chest pain
Oedema peripheral
Pain
Pyrexia

19
2
3
7
1
7
1
1
2
2
2

0.7
0.1
0.1
0.3
0.0
0.3
0.0
0.0
0.1
0.1
0.1

(0.4, 1.1)
(0.0, 0.3)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.3)

HEPATOBILIARY DISORDERS
Acute hepatic failure
Cholecystitis
Cholecystitis acute
Cholelithiasis
Cholelithiasis obstructive
Jaundice
Portosplenomesenteric venous thrombosis
Steatohepatitis

8
1
1
2
1
1
1
1
1

0.3
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0

(0.1, 0.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

IMMUNE SYSTEM DISORDERS
Seasonal allergy

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

INFECTIONS AND INFESTATIONSAppendicitis
Bacteraemia
Bronchitis
Clostridium difficile colitis

39
1
1
1
1

1.4
0.0
0.0
0.0
0.0

(1.0, 1.9)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Ear infection
Endocarditis
Endometritis
Fungal skin infection
Furuncle
Gastritis viral
Gastroenteritis
Gonorrhoea
Helicobacter gastritis
Herpes zoster
Herpes zoster oticus
Meningitis bacterial
Mumps
Onychomycosis
Pneumonia
Post procedural infection
Postoperative abscessSepsisSinusitis bacterial
Subcutaneous abscess
Tooth infection
Urinary tract infection
Viral infection
Wound infection
INJURY, POISONING AND PROCEDURAL COMPLICATIONSAnimal bite
Ankle fracture
Bone contusion
Burns second degree
Burns third degree
Chemical burns of eye
Clavicle fracture
Contusion
Exposure during pregnancy
Facial bones fracture
Fall
Foot fracture

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

1
1
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3
10
1
1

0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.4
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.2)

40
1
2
1
1
1
1
1
3
3
1
10
1

1.4
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.4
0.0

(1.0, 2.0)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.2, 0.7)
(0.0, 0.2)

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Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Hip fracture
Humerus fracture
InjuryLigament rupture
Ligament sprain
Limb injury
Muscle strain
Procedural dizziness
Procedural pain
Radius fracture
Rectal injury
Rib fracture
Road traffic accident
Skin laceration
Thermal burn
Upper limb fracture
Wrist fracture

1
3
1
1
1
1
2
1
4
1
1
2
2
4
1
1
2

0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
0.1
0.0
0.0
0.1
0.1
0.1
0.0
0.0
0.1

(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)

INVESTIGATIONS
Blood cholesterol increased
Blood pressure increased
Body temperature increased
Intraocular pressure increased
SARS-CoV-2 antibody test positive

5
1
1
1
1
1

0.2
0.0
0.0
0.0
0.0
0.0

(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

METABOLISM AND NUTRITION DISORDERS
Diabetes mellitus
Glucose tolerance impaired
Hypercholesterolaemia
Hyperglycaemia
Hyperlipidaemia
Hypertriglyceridaemia
Metabolic syndrome
Type 2 diabetes mellitus
Vitamin D deficiency

13
1
1
2
1
3
1
1
1
2

0.5
0.0
0.0
0.1
0.0
0.1
0.0
0.0
0.0
0.1

(0.2, 0.8)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia
Back pain
Flank pain

27
4
3
1

1.0
0.1
0.1
0.0

(0.6, 1.4)
(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.2)

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Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)Intervertebral disc protrusion
Muscle contracture
Muscle spasms
Musculoskeletal stiffness
Myalgia
Neck pain
Osteoarthritis
Pain in extremity
Periarthritis

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

3
1
1
1
5
1
3
4
1

0.1
0.0
0.0
0.0
0.2
0.0
0.1
0.1
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)
Adenocarcinoma pancreas
Basal cell carcinoma
Brain cancer metastatic
Breast cancer
Fibroma
Haemangioma of skinHormone receptor positive breast cancer
LipomaMalignant melanoma
Metastases to lung
Pancreatic carcinoma metastatic
Prostate cancer
Skin papilloma
Uterine cancer

14

0.5

(0.3, 0.8)

1
2
1
1
1
1
1
1
1
1
1
1
1
1

0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NERVOUS SYSTEM DISORDERS
Carpal tunnel syndrome
Cervical radiculopathy
Dizziness
Dysgeusia
Facial paralysis
Headache
Intracranial aneurysm
Restless legs syndrome
Sciatica
SeizureSeizure like phenomena

18
1
1
3
1
1
7
1
1
1
1
1

0.6
0.0
0.0
0.1
0.0
0.0
0.3
0.0
0.0
0.0
0.0
0.0

(0.4, 1.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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2.7.4 Summary of Clinical Safety

Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

TremorVocal cord paralysis

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS
Abortion spontaneous
Exposure during pregnancy

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

PSYCHIATRIC DISORDERS
Adjustment disorderAnxiety disorder
Bipolar I disorder
Insomnia

4
1
1
1
1

0.1
0.0
0.0
0.0
0.0

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

RENAL AND URINARY DISORDERS
Bladder irritation
Nephrolithiasis
Renal haematoma

5
1
3
1

0.2
0.0
0.1
0.0

(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Endometrial thickening
Endometriosis
Menorrhagia

2
1
1
1

0.1
0.0
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
AsthmaChronic obstructive pulmonary disease
Dyspnoea
Dyspnoea exertional
Epistaxis
Pulmonary embolism
Respiratory tract congestion
Rhinorrhoea
Sleep apnoea syndrome

11
1
1
1
1
1
1
2
2
1

0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.1
0.0

(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Alopecia
Angioedema
Decubitus ulcer
Dermatitis
Dermatitis contact
Hand dermatitis
Necrobiosis lipoidica diabeticorum

14
1
1
1
1
1
1
1

0.5
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.3, 0.8)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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2.7.4 Summary of Clinical Safety

Table 10. Incidence Rates of at Least 1 Adverse Event From Unblinding Date to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received
BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Onycholysis
Rash
Rash maculo-papular
Urticaria

1
1
1
4

0.0
0.0
0.0
0.1

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

SOCIAL CIRCUMSTANCES
Job dissatisfaction
Stress at work

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

SURGICAL AND MEDICAL PROCEDURES
Incisional drainage
Meniscus operation
Metabolic surgery
Radioactive iodine therapy
Tooth extraction

5
1
1
1
1
1

0.2
0.0
0.0
0.0
0.0
0.0

(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

VASCULAR DISORDERS
Aortic aneurysm
Arterial occlusive disease
Deep vein thrombosis
Hot flush
Hypertension
Peripheral vascular disorder

23
2
1
2
1
17
1

0.8
0.1
0.0
0.1
0.0
0.6
0.0

(0.5, 1.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.4, 1.0)
(0.0, 0.2)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from the unblinding date to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s131_all_ex_bnt_p3_saf

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2.7.4 Summary of Clinical Safety

2.7.4.2.4.2.3.2.2. Related Adverse Events by System Organ Class and Preferred Term:
Open-Label Follow-Up Period – Original BNT162b2 Participants (Phase 3, Study
C4591001, Analysis of Adverse Events)
From the unblinding date to the data cutoff date for participants originally randomized to
BNT162b2, the IR of AEs assessed as related by the investigator during the open-label
follow-up period was 0.7 per 100 PY (Table 9). The IRs of related AEs were highest forreactogenicity events and in the SOC of general disorders and administration site conditions(0.5 per 100 PY) reflecting AEs from their initial vaccinations.
One younger participant had a life-threatening SAE of myocardial infarction 71 days after
Dose 2 that was assessed by the investigator as related to study intervention, which lasted
1 day and resolved the same day (see Section 2.7.4.2.4.3.2.3).
2.7.4.2.4.2.4. Blinded Placebo-Controlled and Open-Label Follow-Up Periods From
Dose 1 to 6 Months After Dose 2 – Original BNT162b2 Participants (Phase 3, Study
C4591001)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

2.7.4.2.4.2.4.1. Summary of Adverse Events: Blinded Placebo-Controlled and OpenLabel Follow-Up Periods From Dose 1 to 6 Months After Dose 2 – Original BNT162b2
Participants (Phase 3, Study C4591001)
There were 12,006 participants who had at least 6 months of follow-up (Table 11). There
were 3,454 (28.8%) participants who reported at least 1 AE, and 2,245 (18.7%) participants
reported at least 1 related AE. Severe AEs and SAEs were reported by 2.1% and 1.6%,
respectively. One participant was reported as discontinued because of an AE (not related);
however, this participant remains in the study as the withdrawal was subsequently queriedand corrected as described in Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Errata. There were no deaths during the blinded and open-label follow-up periods in thegroup of original BNT162b2 participants with at least 6 months of follow-up after Dose 2.
When frequencies of AEs for participants with at least 6 months of follow-up time are
examined by time since the second dose, the frequency of AEs and related AEs is 25.8% and18.6% through 1 month after Dose 2 compared with 4.8% and 0.1% from 1 month after
Dose 2 to 6 months after Dose 2 (Table 12). In the first month after vaccination 0.5%
reported SAEs (1 related) and from 1 month to 6 months after Dose 2, the frequency of SAEs
increased to 1.1% with 1 related SAE.
In the younger age group, the number of participants who reported at least 1 AE and 1 related
AE from Dose 1 to 6 months after Dose 2 was 2,013 (30.2%) and 1,386 (20.8%),
respectively. In the older age group, the number of participants who reported at least 1 AE
and 1 related AE from Dose 1 to 6 months after Dose 2 was 1,441 (27.0%) and 859 (16.1%),
respectively.

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2.7.4 Summary of Clinical Safety

Table 11. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2 – Subjects With at Least 6 Months of Follow-up
Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)
nb (%)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Adverse Event
Any event
Relatedc
SevereLife-threatening
Any serious adverse event
Relatedc
SevereLife-threatening
Any adverse event leading to withdrawal
Relatedc
SevereLife-threatening
Death3454 (28.8)2245 (18.7)
248 (2.1)
23 (0.2)
190 (1.6)
2 (0.0)116 (1.0)
23 (0.2)
1 (0.0)0000a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number ofsubjects reporting at least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(14:48)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s091 all pd2 p3 saf2

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Table 12. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by Time Period – Subjects With at Least 6
Months of Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Yearsof Age (Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
Dose 1 to 1 Month Post Dose 2(Na=12006)

After 1 Month Post Dose 2 to 6 Months
Post Dose 2(Na=12006)

nb (%)

nb (%)

Any event3092 (25.8)

572 (4.8)

Relatedc

2239 (18.6)

12 (0.1)

Severe143 (1.2)

110 (0.9)

Life-threatening

8 (0.1)15 (0.1)

Adverse Event

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Any serious adverse event

58 (0.5)

133 (1.1)

Relatedc

1 (0.0)1 (0.0)

Severe34 (0.3)

82 (0.7)

Life-threatening

8 (0.1)15 (0.1)01 (0.0)Relatedc

00

Severe00Life-threatening

0

0

0

0

Any adverse event leading towithdrawal

Deatha. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = numberof subjects reporting at least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 14APR2021(08:45)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA RR/adae s091 all pd2 p3 tp saf2

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2.7.4 Summary of Clinical Safety

2.7.4.2.4.2.4.2. Analysis of Adverse Events: Blinded Placebo-Controlled and OpenLabel Follow-Up Periods From Dose 1 to 6 Months After Dose 2 – Original BNT162b2
Participants (Phase 3, Study C4591001)
2.7.4.2.4.2.4.2.1. Adverse Events by System Organ Class and Preferred Term: Blinded
Placebo-Controlled and Open-Label Follow-Up Periods From Dose 1 to 6 Months After
Dose 2 – Original BNT162b2 Participants (Phase 3, Study C4591001, Analysis ofAdverse Events)
From Dose 1 to 6 Months After Dose 2 during the blinded and open-label follow-up period,3454 (28.8%) original BNT162b2 participants reported at least 1 AE (Table 13). The mostfrequently reported AEs were reactogenicity events.


general disorders and administration site conditions (2016 [16.8%])
musculoskeletal and connective tissue disorders (905 [7.5%])
nervous system disorders (726 [6.0%])
gastrointestinal disorders (407 [3.4%])

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The number of original BNT162b2 participants who reported at least 1 AE from Dose 1 to
6 months after Dose 2 was 2013 (30.2%) and 1441 (27.0%) in the younger and older groups,
respectively.
In the younger versus older BNT162b2 age groups, AE frequencies in above SOCs were:general disorders and administration site conditions (1246 [18.7%] vs 770 [14.4%])
musculoskeletal and connective tissue disorders (539 [8.1%] vs 366 [6.9%])
nervous system disorders (449 [6.7%] vs 277 [5.2%])
gastrointestinal disorders (231 [3.5%] vs 176 [3.3%])

As shown in Table 13, the most frequently reported AEs in the BNT162b2 group were
injection site pain (1191 [9.9%]), pyrexia (633 [5.3%]), chills (606 [5.0%]), fatigue(598 [5.0%]), headache (572 [4.8%]), and myalgia (549 [4.6%]).
When AEs are compared from 1 month after Dose 2 and from 1 month after Dose 2 to
6 months after Dose 2, the frequencies of AEs by most SOCs have decreased or remain thesame with the additional follow-up time. The overall frequency of any AE for participantsfrom 1 month after Dose 2 to 6 months after Dose 2 (4.8%) was decreased from thefrequency during 1 month follow up time after Dose 2 (25.8%).

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)
nb (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Any event3454 (28.8)(28.0, 29.6)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymphadenopathy
Anaemia
Iron deficiency anaemia
Lymph node pain
Leukopenia
Blood loss anaemia
Coagulopathy
Lymphadenopathy mediastinal
Lymphocytosis
Lymphopenia
Neutropenia
Pancytopenia
Splenic infarction
Splenomegaly

70 (0.6)50 (0.4)
7 (0.1)5 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.5, 0.7)
(0.3, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Atrial fibrillation
Tachycardia
Palpitations
Coronary artery disease
Acute myocardial infarction
Angina pectoris
Myocardial infarction
Cardiac failure congestive
Angina unstable
Acute coronary syndrome
Arrhythmia
Arrhythmia supraventricularAtrial flutter
Atrioventricular block first degree
Bradycardia
Bundle branch block right
Cardiac arrest

59 (0.5)
9 (0.1)9 (0.1)7 (0.1)6 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.4, 0.6)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Cardiac disorder
CardiomegalyCoronary artery occlusion
Left ventricular dysfunction
Mitral valve prolapse
Pericarditis
Sinus tachycardia
Supraventricular tachycardia
Ventricular tachycardia

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Congenital cystic kidney disease
Gastrointestinal arteriovenous malformation
Protein S deficiency

3 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
VertigoEar painTinnitus
Vertigo positional
Cerumen impaction
Deafness neurosensory
Ear discomfort
Deafness unilateralHyperacusis
Sudden hearing loss

49 (0.4)
21 (0.2)
8 (0.1)6 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.3, 0.5)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

ENDOCRINE DISORDERS
Hypothyroidism
Hyperthyroidism
Hypogonadism
Thyroid mass
GoitreHyperprolactinaemia
Oestrogen deficiency
Pituitary cyst

15 (0.1)
6 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EYE DISORDERS
Cataract

47 (0.4)
5 (0.0)(0.3, 0.5)
(0.0, 0.1)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Vision blurred
Chalazion
Eye irritation
Eye pain
Macular oedema
Vitreous detachment
Blepharitis
Diplopia
Dry eyeGlaucoma
Retinal tear
Asthenopia
Choroidal neovascularisation
Conjunctival haemorrhage
Corneal irritation
Episcleritis
Eye pruritus
Eyelid oedema
Eyelid pain
Eyelids pruritus
Keratitis
Ophthalmic vein thrombosis
Photophobia
Retinal artery occlusion
Scleral discolouration
Vitreous floaters

5 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GASTROINTESTINAL DISORDERS
NauseaDiarrhoea
Vomiting
Toothache
Abdominal pain
Gastrooesophageal reflux disease
Dyspepsia
Abdominal pain upper
Odynophagia

407 (3.4)
140 (1.2)
123 (1.0)
35 (0.3)
18 (0.1)
15 (0.1)
14 (0.1)
13 (0.1)
10 (0.1)
10 (0.1)(3.1, 3.7)
(1.0, 1.4)
(0.9, 1.2)
(0.2, 0.4)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Constipation
Dental caries
Irritable bowel syndrome
Abdominal distension
Flatulence
Gastritis
Hiatus hernia
Large intestine polyp
Aphthous ulcer
Diverticulum
Food poisoning
Haemorrhoids
ColitisGastritis erosive
Gastrointestinal disorder
Glossodynia
Haematochezia
Impaired gastric emptying
Oral pain
Small intestinal obstruction
Abdominal discomfort
Abdominal pain lower
Abdominal rigidity
Angular cheilitis
Cheilitis
Coeliac disease
Colitis microscopic
Colitis ulcerative
Crohn's disease
Diverticulum intestinal
Dry mouth
Dysphagia
Epiploic appendagitis
Eructation
Faeces soft
Femoral hernia

7 (0.1)6 (0.0)5 (0.0)4 (0.0)4 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Gastric antral vascular ectasia
Gastric ulcer
Gastric ulcer haemorrhage
Gastrointestinal haemorrhage
Gastrointestinal pain
Gingival pain
Glossitis
Haematemesis
Haemorrhoidal haemorrhage
Hypoaesthesia oralHypoaesthesia teeth
Inguinal hernia
Internal hernia
Intestinal obstruction
Intestinal polypIntra-abdominal fluid collection
Lip oedema
Noninfective gingivitis
Obstructive pancreatitis
Oesophageal spasm
Oral discomfort
Oral lichenoid reaction
Pancreatic calcification
Pancreatitis
Parotid duct obstruction
Rectal haemorrhage
Rectal polyp
Retching
Stomatitis
Swollen tongue
Tongue oedema
Tongue pruritus
Tongue ulceration
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONSInjection site pain
Pyrexia

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2016 (16.8)
1191 (9.9)
633 (5.3)(16.1, 17.5)(9.4, 10.5)(4.9, 5.7)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
ChillsFatigue
Pain
Injection site erythema
Injection site swelling
MalaiseAsthenia
Injection site pruritus
Chest pain
Influenza like illness
Injection site bruising
Axillary pain
Injection site warmthFeeling hot
Injection site induration
Oedema peripheral
Peripheral swelling
Injection site oedema
Non-cardiac chest pain
Adverse drug reaction
Cyst
Face oedema
Injection site discomfort
Injection site haematoma
Injection site nodule
Injection site papule
Swelling
Application site erythema
Application site pain
Application site pruritus
Application site reaction
Chest discomfort
Drug withdrawal syndrome
Illness
Induration
Inflammation

606 (5.0)
598 (5.0)
277 (2.3)
91 (0.8)60 (0.5)
46 (0.4)
20 (0.2)
19 (0.2)
14 (0.1)
10 (0.1)
8 (0.1)6 (0.0)6 (0.0)5 (0.0)5 (0.0)5 (0.0)4 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(4.7, 5.5)
(4.6, 5.4)
(2.0, 2.6)
(0.6, 0.9)
(0.4, 0.6)
(0.3, 0.5)
(0.1, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Injection site discolouration
Injection site haemorrhage
Injection site hyperaesthesia
Injection site irritation
Injection site lymphadenopathy
Injection site mass
Injection site paraesthesia
Injection site rash
Injection site reaction
Medical device pain
Sensation of foreign body
Shoulder injury related to vaccine administration
Sluggishness
Temperature intolerance
ThirstVaccination site induration
Vascular stent occlusion
Vessel puncture site bruise
Vessel puncture site haematoma

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

HEPATOBILIARY DISORDERS
Cholelithiasis
Biliary colic
Cholecystitis acute
Bile duct stone
Biliary dyskinesia
Cholecystitis
Cholelithiasis obstructive
Gallbladder disorder
Hepatic steatosis
Jaundice
Portosplenomesenteric venous thrombosis
Steatohepatitis

21 (0.2)
7 (0.1)4 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Seasonal allergy
Drug hypersensitivity
Hypersensitivity

15 (0.1)
6 (0.0)2 (0.0)2 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Allergy to arthropod bite
Allergy to arthropod sting
Anaphylactic reaction
Food allergy
Jarisch-Herxheimer reaction

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INFECTIONS AND INFESTATIONSUrinary tract infection
Tooth infection
Sinusitis
Appendicitis
Herpes zoster
Cellulitis
Conjunctivitis
Cystitis
Ear infection
Diverticulitis
Gastroenteritis
Tooth abscessHordeolum
Upper respiratory tract infection
Folliculitis
Rhinitis
Nasopharyngitis
Oral herpes
Otitis externa
Vulvovaginal mycotic infection
Fungal skin infection
Gingivitis
Onychomycosis
Paronychia
Pharyngitis streptococcal
Pneumonia
Pyelonephritis
Vulvovaginal candidiasis
Device related infection
Herpes simplex

295 (2.5)
57 (0.5)
20 (0.2)
16 (0.1)
10 (0.1)
10 (0.1)
9 (0.1)8 (0.1)8 (0.1)8 (0.1)7 (0.1)7 (0.1)7 (0.1)6 (0.0)6 (0.0)5 (0.0)5 (0.0)4 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)(2.2, 2.7)
(0.4, 0.6)
(0.1, 0.3)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Influenza
Kidney infection
Laryngitis
Localised infection
Oral candidiasis
Otitis media
Otitis media acute
Periodontitis
PustuleRash pustular
SepsisSinusitis bacterial
Skin infection
Viral infection
Abscess
Abscess neck
Abscess oral
Acute sinusitis
Appendicitis perforated
Arthritis bacterial
Bacteraemia
Bacterial blepharitis
Bacterial sepsis
Bacterial vaginosis
Bacterial vulvovaginitis
Bartholinitis
Bone abscess
Bronchitis
Cellulitis orbital
Chronic sinusitis
Clostridium difficile colitis
Empyema
Endocarditis
Escherichia urinary tract infection
Eye infection
Fungal infection

2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Furuncle
Gangrene
Gastroenteritis viral
Gastrointestinal infection
Genital herpes simplex
Helicobacter gastritis
Helicobacter infection
Herpes zoster oticus
Impetigo
Infected bite
Injection site abscess
Mastoiditis
Meningitis bacterial
Mumps
Papilloma viral infection
Parasitic gastroenteritis
Penile infection
Peritoneal abscess
Peritonitis
Peritonsillar abscessPharyngitis
Pharyngotonsillitis
Pilonidal cyst
Postoperative abscessRespiratory tract infection viral
Sialoadenitis
Staphylococcal infection
Subcutaneous abscessTinea versicolour
Varicella
Vulval abscess
Vulvovaginitis
Wound infection
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
FallExposure during pregnancy

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)207 (1.7)
47 (0.4)
22 (0.2)(1.5, 2.0)
(0.3, 0.5)
(0.1, 0.3)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Muscle strain
Ligament sprain
Contusion
Procedural pain
Road traffic accident
Skin laceration
Arthropod bite
Limb injury
Tooth fracture
Ankle fracture
Chest injury
Foot fracture
Hand fracture
Joint dislocation
Skin abrasion
Joint injury
Meniscus injury
Wrist fracture
Animal bite
Arthropod sting
Burns second degree
Cervical vertebral fracture
Facial bones fracture
Humerus fracture
Patella fracture
Tibia fracture
Upper limb fracture
Vaccination complication
Concussion
Craniocerebral injury
Ligament rupture
Radius fracture
Rib fracture
Thermal burnBone contusion
Bone fissure

15 (0.1)
13 (0.1)
12 (0.1)
11 (0.1)
11 (0.1)
11 (0.1)
7 (0.1)7 (0.1)6 (0.0)5 (0.0)5 (0.0)5 (0.0)5 (0.0)5 (0.0)5 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Burn oral cavity
Burns first degree
Burns third degree
Cartilage injury
Chemical burns of eye
Corneal abrasion
Eyelid injury
Fibula fracture
Foreign body in eye
Fractured sacrum
Head injury
Hip fracture
Jaw fracture
Limb fracture
Limb traumatic amputation
Maternal exposure before pregnancy
Maternal exposure during pregnancy
Muscle contusion
Muscle rupture
Overdose
Pelvic fracture
Penis injury
Post concussion syndrome
Post procedural discomfort
Post procedural swelling
Procedural dizzinessSpinal compression fracture
Spinal cord injury cervical
Spinal fracture
Stress fracture
Subdural haematoma
Sunburn
Traumatic intracranial haemorrhage
Ulna fracture
INVESTIGATIONS
Body temperature increased

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

94 (0.8)50 (0.4)(0.6, 1.0)
(0.3, 0.5)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Blood glucose increased
SARS-CoV-2 antibody test positive
Blood pressure increased
Blood cholesterol increased
Alanine aminotransferase increased
Blood thyroid stimulating hormone increased
Weight increased
Aspartate aminotransferase increased
Blood creatinine decreased
Blood glucose abnormal
Blood immunoglobulin E increased
Blood potassium decreased
Blood triglycerides increased
Body temperature decreased
C-reactive protein
Cardiac stress test abnormal
Electrocardiogram QT prolonged
Fractional exhaled nitric oxide increased
Glomerular filtration rate decreased
Haemoglobin decreased
Heart rate increased
Intraocular pressure increased
Liver function test increased
Lymphocyte count decreased
Mean cell volume decreased
Platelet count decreased
Respiratory rate increased
Troponin increased
Weight decreased

8 (0.1)5 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

METABOLISM AND NUTRITION DISORDERS
Decreased appetite
Hyperlipidaemia
Type 2 diabetes mellitus
Vitamin D deficiency
Hypercholesterolaemia
Dyslipidaemia

81 (0.7)
15 (0.1)
9 (0.1)9 (0.1)8 (0.1)6 (0.0)5 (0.0)(0.5, 0.8)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Glucose tolerance impaired
Gout
Hyperglycaemia
Hypertriglyceridaemia
Hypoglycaemia
Hypokalaemia
Dehydration
Hyperkalaemia
Hyperuricaemia
Obesity
Diabetes mellitus
Diabetes mellitus inadequate control
Diabetic ketoacidosis
Hypocalcaemia
Hypocholesterolaemia
Insulin resistanceMetabolic syndrome
Polydipsia
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Myalgia
Arthralgia
Pain in extremity
Back pain
Neck pain
Muscle spasms
Osteoarthritis
Tendonitis
Musculoskeletal stiffness
Intervertebral disc protrusion
Arthritis
Bursitis
Muscular weakness
Musculoskeletal chest pain
Periarthritis
Musculoskeletal discomfort
Intervertebral disc degeneration

4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)905 (7.5)
549 (4.6)
153 (1.3)
93 (0.8)62 (0.5)
20 (0.2)
19 (0.2)
14 (0.1)
9 (0.1)8 (0.1)6 (0.0)5 (0.0)5 (0.0)5 (0.0)5 (0.0)5 (0.0)4 (0.0)3 (0.0)(7.1, 8.0)
(4.2, 5.0)
(1.1, 1.5)
(0.6, 0.9)
(0.4, 0.7)
(0.1, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Joint stiffness
Muscle contracture
Rotator cuff syndrome
Arthropathy
Coccydynia
Costochondritis
Flank pain
Joint range of motion decreased
Limb discomfort
Muscle twitching
Musculoskeletal pain
Pain in jaw
Plantar fasciitis
Spinal osteoarthritis
Tenosynovitis stenosans
Bone disorder
Bone pain
Groin pain
Intervertebral disc compression
Joint effusion
Joint instability
Joint swelling
Mobility decreased
Muscle fatigue
Muscle tightness
Osteochondritis
Osteopenia
Psoriatic arthropathy
Spinal stenosis
Spondylitis
Synovial cyst
Temporomandibular joint syndrome
Torticollis
Trigger finger
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)

3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

53 (0.4)(0.3, 0.6)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Prostate cancer
Basal cell carcinoma
LipomaMalignant melanoma
Breast cancer
Invasive ductal breast carcinoma
Skin papilloma
Transitional cell carcinoma
Acute myeloid leukaemia
Adenocarcinoma pancreas
Adenoma benign
Adrenal gland cancer
Benign breast neoplasm
Benign hydatidiform mole
Benign uterine neoplasm
Bladder cancer
Borderline serous tumour of ovary
Brain cancer metastatic
Breast cancer in situ
Carcinoid tumour of the stomach
Chondroma
Colon adenoma
Fibroma
Gallbladder cancer stage II
Gastric cancer
Malignant melanoma of eyelid
Meningioma benign
Non-small cell lung cancer stage IV
Seborrhoeic keratosis
Skin cancer
Squamous cell carcinoma
Squamous cell carcinoma of skin
Thyroid cancer
Uterine cancer
Uterine leiomyoma
NERVOUS SYSTEM DISORDERS

5 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)726 (6.0)(5.6, 6.5)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
HeadacheDizziness
Paraesthesia
Lethargy
Migraine
Sciatica
Tension headache
SyncopePresyncope
TremorDysgeusia
Somnolence
Disturbance in attention
Facial paralysis
Hypoaesthesia
Sinus headache
Subarachnoid haemorrhage
Burning sensation
Cerebrovascular accident
Cervical radiculopathy
Dizziness postural
Migraine without aura
Nerve compression
Optic neuritis
Restless legs syndrome
SeizureTransient ischaemic attack
Aphasia
Carpal tunnel syndrome
Depressed level of consciousness
Dyskinesia
Hyperaesthesia
Idiopathic intracranial hypertension
Intracranial aneurysm
Ischaemic stroke
Neuralgia

572 (4.8)
43 (0.4)
15 (0.1)
14 (0.1)
14 (0.1)
9 (0.1)9 (0.1)8 (0.1)6 (0.0)6 (0.0)5 (0.0)4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(4.4, 5.2)
(0.3, 0.5)
(0.1, 0.2)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Parosmia
Periodic limb movement disorder
Peripheral nerve lesion
Peripheral sensory neuropathy
Post herpetic neuralgia
Radiculopathy
Seizure like phenomena
Toxic encephalopathy
Transient global amnesia
Uraemic encephalopathy
Vocal cord paralysis

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS
Abortion spontaneous
Exposure during pregnancy

3 (0.0)2 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

PRODUCT ISSUES
Device connection issue

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

PSYCHIATRIC DISORDERS
Insomnia
Anxiety
Depression
Anxiety disorder
Abnormal dreams
Attention deficit hyperactivity disorder
Irritability
Sleep disorder
Disorientation
Nightmare
Generalised anxiety disorder
Libido increased
Panic attack
Restlessness
Suicide attempt

65 (0.5)
17 (0.1)
16 (0.1)
11 (0.1)
4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.4, 0.7)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

RENAL AND URINARY DISORDERS
Nephrolithiasis
Dysuria42 (0.3)
11 (0.1)
6 (0.0)(0.3, 0.5)
(0.0, 0.2)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Pollakiuria
Haematuria
Acute kidney injury
Bladder spasm
Renal colic
Urinary retention
Bladder irritation
Chronic kidney disease
Hypertonic bladder
Micturition urgency
Obstructive nephropathy
Renal cyst
Renal haematoma
Subcapsular renal haematoma
Urethral stenosis
Urinary tract obstruction
Vesical fistula
REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Dysmenorrhoea
Ovarian cyst
Benign prostatic hyperplasia
Breast pain
Endometriosis
Genital erythema
Menorrhagia
Menstruation irregularAmenorrhoea
Breast hyperplasia
Cervical dysplasia
Dysfunctional uterine bleeding
Endometrial thickening
Haematospermia
Mammary duct ectasia
Menometrorrhagia
Metrorrhagia
Pelvic pain

5 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

36 (0.3)
4 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Polycystic ovaries
Postmenopausal haemorrhage
Prostatitis
Prostatomegaly
Pruritus genital
Scrotal pain
Testicular pain
Testicular torsion
Uterine prolapse
Vaginal haemorrhage
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Oropharyngeal pain
Nasal congestion
Cough
Rhinorrhoea
Rhinitis allergic
AsthmaDyspnoea
Pulmonary embolism
Sleep apnoea syndrome
Throat irritation
Upper-airway cough syndrome
Paranasal sinus discomfort
Chronic obstructive pulmonary disease
Epistaxis
Asthmatic crisis
Bronchospasm
Nasal polyps
Productive coughRespiratory tract congestion
Sinus congestion
Upper respiratory tract congestion
Wheezing
Allergic sinusitis
Atelectasis
Dry throat

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

145 (1.2)
24 (0.2)
21 (0.2)
17 (0.1)
12 (0.1)
9 (0.1)8 (0.1)6 (0.0)6 (0.0)5 (0.0)5 (0.0)5 (0.0)4 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)(1.0, 1.4)
(0.1, 0.3)
(0.1, 0.3)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Dyspnoea exertional
Emphysema
Haemoptysis
Interstitial lung disease
Nasal septum deviation
Oropharyngeal discomfort
Paranasal sinus hypersecretion
Pleurisy
Pneumonitis
Pneumothorax
Reflux laryngitis
Respiratory failure
Sneezing
SnoringTonsillar hypertrophy
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash
Hyperhidrosis
Pruritus
Dermatitis contact
Urticaria
Night sweats
Rash pruritic
Erythema
Dermal cyst
Dermatitis
EczemaAcne
Actinic keratosis
Dermatitis allergic
Rash maculo-papular
Alopecia
Acne cystic
Angioedema
Cold sweat
Dermatitis exfoliative

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

153 (1.3)
35 (0.3)
16 (0.1)
15 (0.1)
11 (0.1)
11 (0.1)
8 (0.1)6 (0.0)5 (0.0)4 (0.0)4 (0.0)4 (0.0)3 (0.0)3 (0.0)3 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(1.1, 1.5)
(0.2, 0.4)
(0.1, 0.2)
(0.1, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Diabetic footDry skin
Ecchymosis
Erythema nodosum
Hand dermatitis
HangnailIntertrigo
MaculeOnycholysis
Onychomadesis
Pain of skin
PapulePityriasis
Pseudofolliculitis
Psoriasis
PurpuraRash erythematous
Rash papular
Rosacea
Skin discolouration
Skin irritation
Skin ulcer
Transient acantholytic dermatosis

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SOCIAL CIRCUMSTANCESHigh risk sexual behaviour
Miscarriage of partner

2 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

SURGICAL AND MEDICAL PROCEDURES
Dental implantation
Tooth extraction
Wisdom teeth removal
Botulinum toxin injection
Cardioversion
Carpal tunnel decompression
Drug titration
Endodontic procedure
Facet joint block

29 (0.2)
5 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.2, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Finger amputation
Gingival operation
Inguinal hernia repair
Lacrimal duct procedure
Mammoplasty
Meniscus operation
Metabolic surgery
Open reduction of fracture
Postoperative care
Radioactive iodine therapy
Retinal operation
Rotator cuff repair
Sclerotherapy

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS
Hypertension
Deep vein thrombosis
Hot flush
Aortic aneurysm
Haematoma
Flushing
Hypotension
Aortic dilatation
Arterial occlusive disease
Essential hypertension
Intermittent claudication
Lymphorrhoea
Peripheral vascular disorder
Systolic hypertension
Thrombophlebitis superficial
Varicose vein

78 (0.6)
48 (0.4)
6 (0.0)6 (0.0)3 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.5, 0.8)
(0.3, 0.5)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 13. Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1
to 6 Months After Dose 2, by System Organ Class and Preferred Term –Subjects With at Least 6 Months of Follow-up Time After Dose 2 – Phase
2/3 Subjects ≥16 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s130 all bnt pd2 p3 saf

2.7.4.2.4.2.4.2.2. Related Adverse Events by System Organ Class and Preferred Term:
Blinded Placebo-Controlled and Open-Label Follow-Up Periods From Dose 1 to 6
Months After Dose 2 – Original BNT162b2 Participants (Phase 3, Study C4591001,
Analysis of Adverse Events)
From Dose 1 to 6 Months After Dose 2 during the blinded and open-label follow-up period,
AEs assessed as related by the investigator during the blinded and open-label follow-up
period were reported by 18.7% of participants in the BNT162b2 group (Table 11). Most
related AEs were reactogenicity events and in the SOC of general disorders andadministration site conditions (1944 [16.2%]).
The AE of lymphadenopathy in 29 (0.2%) participants was assessed by the investigator as
related to study intervention.
Related AEs in the younger and older age groups were reported in 20.8% and 16.1% oforiginal BNT162b2 participants.
2.7.4.2.4.2.5. Open-Label Follow-Up Period – Original Placebo Participants Who Then
Received BNT162b2
2.7.4.2.4.2.5.1. Summary of Adverse Events: Open-Label Follow-Up Period – Original
Placebo Participants Who Then Received BNT162b2 (Phase 3, Study C4591001)
Overall, there are 19,525 original placebo participants who then were unblinded and received
BNT162b2. An overview of AEs after vaccination with BNT162b2 to the data cutoff date forplacebo participants who received BNT162b2 during the open-label follow-up period ispresented in Table 14. The IRs for any AE and at least 1 related AE were 205.4 per 100 PY
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and 189.5 per 100 PY, respectively. IRs of severe AEs, SAEs, and AEs leading to withdrawal
were 6.0 per 100 PY, 2.7 per 100 PY, and 0.8 per 100 PY. The IR for discontinuations
because of related AEs was 0.5 per 100 PY, and 2 participants died (Section 2.7.4.2.4.3.1).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The IRs in Table 7 include all AEs reported for these participants including AEs reported
while on placebo. Additionally, all of these placebo participants received open-label
BNT162b2 and the exposure time is shorter for placebo participants who received
BNT162b2 than those who originally were randomized to BNT162b2 (23.8 per 100 PY vs83.4 per 100 PY, respectively [Table 14 and Table 7]). As expected, in comparison toparticipants randomized to BNT162b2 from Dose 1 to the unblinding date, the IR for any AE
and at least 1 related AE and severe AE for participants who originally received placebo andthen received BNT162b2 are greater (205.4 per 100 PY, 189.5 per 100 PY, 6.0 per 100 PY)
than the IRs (83.2 per 100 PY, 62.9 per 100 PY, 4.3 per 100 PY) for participants who
originally were randomized to BNT162b2, respectively (Table 14 and Table 7). However, theIRs for life-threatening AE, SAE, AEs leading to withdrawal and deaths were similar (0.5 per
100 PY, 2.7 per 100 PY, 0.8 per 100 PY, 0.1 per 100 PY vs 0.6 per 100 PY, 3.2 per 100 PY,
0.5 per 100 PY, 0.2 per 100 PY, respectively). There was 1 related SAE of anaphylactoid
reaction for a placebo participant who was vaccinated with BNT162b2 (seeSection 2.7.4.2.4.3.2.5).
The IRs of AEs for original placebo participants who then received BNT162b2 wereobserved by baseline SARS CoV-2 positive and negative status subgroups. Overall, the IRs
for AEs were similar between the baseline positive (222.9 per 100 PY; 95% CI: 186.5, 264.3)
compared to baseline negative (205 per 100 PY; 95% CI 199.6, 211.3). There were 2 SAEs
(not related), 1 AE leading to withdrawal and no deaths in the baseline positive group.

Table 14. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021) – Open-Label Follow-up Period – Subjects Who
Originally Received Placebo and Then Received BNT162b2 After
Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

Adverse Eventnc

Any event
Relatedf
SevereLife-threatening
Any serious adverse event
Relatedf
SevereLife-threatening
Any adverse event leading to withdrawal

4885
4508
142
11
65
1
37
11
19

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)
205.4
189.5
6.0
0.5
2.7
0.0
1.6
0.5
0.8

(199.6, 211.2)(184.0, 195.1)(5.0, 7.0)
(0.2, 0.8)
(2.1, 3.5)
(0.0, 0.2)
(1.1, 2.1)
(0.2, 0.8)
(0.5, 1.2)

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Table 14. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021) – Open-Label Follow-up Period – Subjects Who
Originally Received Placebo and Then Received BNT162b2 After
Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)

Adverse Eventnc

Relatedf
SevereLife-threatening
Death

12
2
4
2

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)
0.5
0.1
0.2
0.1

(0.3, 0.9)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.3)

Note: Dose 3 = First dose of BNT162b2 (30 μg).
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 3 to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = number ofsubjects reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s092_cr_cut_p3x_saf

2.7.4.2.4.2.5.2. Analysis of Adverse Events: Open-Label Follow-Up Period – Original
Placebo Participants Who Then Received BNT162b2 (Phase 3, Study C4591001)
2.7.4.2.4.2.5.2.1. Adverse Events by System Organ Class and Preferred Term: OpenLabel Follow-Up Period – Original Placebo Participants Who Then Received
BNT162b2 (Phase 3, Study C4591001, Analysis of Adverse Events)
From vaccination with BNT162b2 for placebo participants to the data cutoff date during theopen-label follow-up period, the IR for participants who reported at least 1 AE was 205.4 per
100 PY (Table 15).
Most AEs reported from Dose 3 (first dose of BNT162b2) to the data cutoff date were in
SOCs with reactogenicity events.


general disorders and administration site conditions (175.3 per 100 PY)
musculoskeletal and connective tissue disorders (52.3 per 100 PY)
nervous system disorders (50.5 per 100 PY)
gastrointestinal disorders (14.3 per 100 PY)

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As shown in Table 15, the most frequently reported AEs (IRs) overall were injection site pain
(123.8 per 100 PY), fatigue (58.0 per 100 PY), headache (46.6 per 100 PY), chills (41.8 per
100 PY), myalgia (38.9 per 100 PY), and pyrexia (38.1 per 100 PY).
After participants who originally received placebo were unblinded and then received
BNT162b2 after unblinding, events related to reactogenicity were not reported using an
e-diary but were instead reported as AEs. An analysis was conducted to evaluate if theimbalance in AEs observed from Dose 3 to the unblinding date was attributed toreactogenicity events. The analysis examined the AEs reported within 7 days after each dose
(Dose 3 and Dose 4), which represented the reactogenicity reporting period.
PTs reported from Dose 3 to 7 days after Dose 3 and from Dose 4 to 7 days after Dose 4 in
the SOCs of general disorders and administration site conditions (injection site pain, chills,
fatigue, and pyrexia), musculoskeletal and connective tissue disorders (myalgia), and nervous
system disorders (headache) represented the majority of PTs reported in those SOCs.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Allergy to vaccine, anaphylactoid reaction, and deep vein thrombosis were reported in
1 participant each from Dose 3 to 7 days after Dose 3.
One participant reported an AE of Grade 2 allergy to vaccine, which occurred on the
day of Dose 3 vaccination, had a duration of 2 days, and resolved; this AE wasassessed by the investigator as related to the study intervention.

One participant with an ongoing medical history significant for drug hypersensitivity
and food and seasonal allergies reported a life-threatening SAE of anaphylactoid
reaction, which occurred 2 days after Dose 3 and was resolved that same day; thisSAE was assessed by the investigator as related to the study intervention(Section 2.7.4.2.4.3.4.1.1).



One participant with a past medical history significant for deep vein thrombosis,
hypertension, pulmonary arterial hypertension, right ventricular enlargement,
hypercholesteremia, artherosclerosis and bilateral peripheral neuropathy reported a
Grade 2 SAE of deep vein thrombosis (lower right extremity) and Grade 1 SAE of
pulmonary embolism, which both occurred 2 days after Dose 3, had both resolved
with a duration of 3 days; both SAEs were assessed by the investigator as not related
to the study intervention.

In addition to analysis of AEs corresponding to e-diary terms, consideration was given to
additional AEs that were reported within 7 days after Dose 3 or Dose 4 such as pain in
extremity, decreased appetite, lethargy, asthenia, malaise, night sweats, and hyperhidrosis.
Similar to the analysis that examined these events 7 days within Dose 1 and Dose 2 of
BNT162b2 in blinded follow-up (Section 2.7.4.2.4.2.1.2.1), these events reported in openlabel follow-up are interpreted as attributable to the experience of local reactions andsystemic events after vaccination with Dose 3 and Dose 4 (first and second dose of
BNT162b2).

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BNT162b2
2.7.4 Summary of Clinical Safety

These results are consistent with the pattern seen during the blinded placebo-controlled
follow-up period from Dose 1 to 1 month after Dose 2 (Section 2.7.4.2.4.2.1.2.1), which
confirms that the greater rates of AEs observed overall in the BNT162b2 group comparedwith the placebo group were largely attributable to reactogenicity events for that time period.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)No clinically meaningful differences in IRs of AEs for original placebo participants who thenreceived BNT162b2 were observed by baseline SARS CoV-2 positive (222.9 per 100 PY)
and negative (205.4 per 100 PY) status subgroups. The IR for original baseline positive
placebo participants who then received BNT162b2 was 222.9 per 100 PY (95% CI: 186.5,
264.3) which was similar to baseline negative placebo participants who then received
BNT162b2 is 205.4 per 100 PY (95% CI: 199.6, 211.3). The IR between other SOC weresimilar in the baseline positive and baseline negative groups except for the musculoskeletal
SOC which was higher in the baseline positive group. However, it was driven by myalgia
64.2 per 100 PY (95% CI: 45.4, 88.1) in baseline positive participants compared to 38.3 per
100 PY (95% CI: 35.8, 40.9) in baseline negative participants.

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event

4885

205.4

(199.6, 211.2)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Anaemia
Coagulopathy
Iron deficiency anaemia
Lymph node pain
Lymphadenitis
Lymphadenopathy

88
2
1
2
6
2
76

3.7
0.1
0.0
0.1
0.3
0.1
3.2

(3.0, 4.6)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.3)
(2.5, 4.0)

CARDIAC DISORDERS
Acute myocardial infarction
Angina pectoris
Arrhythmia
Arteriospasm coronary
Atrial fibrillation
Atrial flutter
Cardiac failure congestive
Cardio-respiratory arrest
Cardiovascular disorder
Coronary artery disease
Ischaemic cardiomyopathy
Myocardial infarction
Palpitations
Supraventricular tachycardia
Tachycardia

17
1
1
1
1
5
1
1
1
1
1
1
1
1
1
2

0.7
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1

(0.4, 1.1)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Atrial septal defect
BRCA2 gene mutation
Factor II mutation
Hypertrophic cardiomyopathy

4
1
1
1
1

0.2
0.0
0.0
0.0
0.0

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

EAR AND LABYRINTH DISORDERS
Cerumen impaction
Deafness neurosensory
Deafness unilateral
Ear discomfort

18
1
1
1
1

0.8
0.0
0.0
0.0
0.0

(0.4, 1.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)Ear pain
Eustachian tube dysfunction
Hypoacusis
Meniere's disease
Sudden hearing loss
Tinnitus
Vertigo

4
2
1
1
1
2
6

0.2
0.1
0.0
0.0
0.0
0.1
0.3

(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.5)

ENDOCRINE DISORDERS
Hypothyroidism
Thyroid disorderThyroid mass

4
2
1
1

0.2
0.1
0.0
0.0

(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

EYE DISORDERS
Blepharitis
Cataract
Conjunctival haemorrhage
Dacryostenosis acquired
Diplopia
Dry eye
Erythema of eyelid
Eye irritation
Eye painEye swelling
Keratitis
Lacrimation increased
Meibomianitis
Ocular discomfort
Visual impairment
Vitreous floaters

26
1
4
1
1
1
1
1
1
5
1
2
3
1
1
1
1

1.1
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.2
0.0
0.1
0.1
0.0
0.0
0.0
0.0

(0.7, 1.6)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

GASTROINTESTINAL DISORDERS
Abdominal discomfort
Abdominal distension
Abdominal pain
Abdominal pain lower
Abdominal pain upper
Anal fistulaAnal prolapse

339
4
1
12
2
13
2
1

14.3
0.2
0.0
0.5
0.1
0.5
0.1
0.0

(12.8, 15.9)(0.0, 0.4)
(0.0, 0.2)
(0.3, 0.9)
(0.0, 0.3)
(0.3, 0.9)
(0.0, 0.3)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Chronic gastritis
Constipation
Dental caries
Diarrhoea
Dry mouth
Duodenitis
Dyspepsia
Gastric ulcer
Gastritis
Gastrointestinal haemorrhage
Gastrointestinal necrosis
Gastrointestinal sounds abnormal
Gastrooesophageal reflux disease
Gingival bleeding
Haemorrhoids
Hiatus hernia
Hyperaesthesia teeth
Hypoaesthesia oral
Intestinal obstruction
Intestinal ulcer perforation
Irritable bowel syndrome
Large intestine polyp
NauseaOedema mouth
Oral mucosal blistering
Oral pain
Oral pruritus
Pancreatitis acute
Retching
Small intestinal obstruction
Stomatitis
Submaxillary gland enlargement
Tongue disorderTongue oedema
ToothacheUmbilical hernia

1
4
1
91
3
1
5
1
5
1
1
1
7
1
1
2
1
1
1
1
2
1
160
1
1
1
1
2
1
1
2
1
1
1
1
1

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

0.0
0.2
0.0
3.8
0.1
0.0
0.2
0.0
0.2
0.0
0.0
0.0
0.3
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.0
6.7
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(3.1, 4.7)
(0.0, 0.4)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(5.7, 7.9)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vomiting
GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONSApplication site pain
Asthenia
Axillary pain
Chest discomfort
Chest pain
ChillsCrying
Discomfort
Drug withdrawal syndrome
Facial pain
Fatigue
Feeling abnormal
Feeling cold
Feeling hot
Gait disturbance
Implant site pain
Inflammation
Influenza like illness
Injection site bruising
Injection site discomfort
Injection site erythema
Injection site haematoma
Injection site haemorrhage
Injection site hypersensitivity
Injection site hypoaesthesia
Injection site induration
Injection site irritation
Injection site lymphadenopathy
Injection site mass
Injection site nodule
Injection site oedema
Injection site pain
Injection site pruritus

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)48

2.0(1.5, 2.7)

4169

175.3

(170.0, 180.7)

2
36
3
2
4
994
1
2
1
1
1379
6
2
6
1
1
1
1
16
3
66
2
1
1
2
1
1
1
1
2
2
2944
18

0.1
1.5
0.1
0.1
0.2
41.8
0.0
0.1
0.0
0.0
58.0
0.3
0.1
0.3
0.0
0.0
0.0
0.0
0.7
0.1
2.8
0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.1
0.1
123.8
0.8

(0.0, 0.3)
(1.1, 2.1)
(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.4)
(39.2, 44.5)(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(55.0, 61.1)(0.1, 0.5)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.4, 1.1)
(0.0, 0.4)
(2.1, 3.5)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(119.3, 128.3)(0.4, 1.2)

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Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

Injection site rash
Injection site reaction
Injection site swelling
Injection site urticaria
Injection site warmth
MalaiseNon-cardiac chest pain
Oedema peripheral
Pain
Pelvic mass
Peripheral swelling
Pyrexia
Swelling
Swelling face
Vaccination site pain
Vaccination site reaction
Vessel puncture site haematoma

4
2
65
1
3
83
1
2
394
1
7
906
3
4
3
1
1

0.2
0.1
2.7
0.0
0.1
3.5
0.0
0.1
16.6
0.0
0.3
38.1
0.1
0.2
0.1
0.0
0.0

(0.0, 0.4)
(0.0, 0.3)
(2.1, 3.5)
(0.0, 0.2)
(0.0, 0.4)
(2.8, 4.3)
(0.0, 0.2)
(0.0, 0.3)
(15.0, 18.3)(0.0, 0.2)
(0.1, 0.6)
(35.6, 40.6)(0.0, 0.4)
(0.0, 0.4)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)

HEPATOBILIARY DISORDERS
Cholecystitis
Cholelithiasis
Hepatitis acute

3
1
1
1

0.1
0.0
0.0
0.0

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

IMMUNE SYSTEM DISORDERS
Allergy to vaccine
Anaphylactoid reaction
Hypersensitivity
Seasonal allergy

7
1
1
1
4

0.3
0.0
0.0
0.0
0.2

(0.1, 0.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

INFECTIONS AND INFESTATIONS
Abscess
Appendicitis perforated
Asymptomatic bacteriuria
COVID-19 pneumonia
Candida infection
Cellulitis
Chlamydial infection
Clostridium difficile infection
Conjunctivitis

136
1
1
1
1
1
3
1
1
6

5.7
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.3

(4.8, 6.8)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)

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Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Cystitis
Demodicidosis
Diverticulitis
Ear infection
Eye infection
Focal peritonitis
Folliculitis
Fungal skin infection
Genital herpes
Genital herpes simplex
Helicobacter gastritis
Herpes simplex
Herpes zoster
Hordeolum
Infected cyst
Infection
Labyrinthitis
Localised infection
Mastitis
Onychomycosis
Oral candidiasis
Oral herpes
Osteomyelitis
Otitis externa
Otitis media
Pelvic abscess
Pneumonia
Postoperative wound infection
Rhinitis
Sinusitis
Subcutaneous abscess
Suspected COVID-19
Taeniasis
Tinea infection
Tinea pedis
Tonsillitis

1
1
2
8
1
1
1
3
1
2
1
2
8
2
1
1
1
2
1
1
1
3
1
2
2
1
2
1
2
7
2
1
1
1
2
2

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

0.0
0.0
0.1
0.3
0.0
0.0
0.0
0.1
0.0
0.1
0.0
0.1
0.3
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.1
0.0
0.1
0.1
0.0
0.1
0.0
0.1
0.3
0.1
0.0
0.0
0.0
0.1
0.1

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.7)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.6)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)

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2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)Tooth abscess
Tooth infection
Urinary tract infection
Urosepsis
Vulvitis
Vulvovaginal candidiasis
Vulvovaginal mycotic infection
INJURY, POISONING AND PROCEDURAL COMPLICATIONSAnimal bite
Ankle fracture
Arthropod bite
Chest injury
Contusion
Corneal abrasion
Exposure during pregnancy
Eye contusion
Facial bones fracture
Fall
Fibula fracture
Foot fracture
Frostbite
Hand fracture
Head injury
Injection related reaction
Joint dislocation
Ligament injury
Ligament sprain
Limb injury
Lip injury
Lower limb fracture
Maternal exposure during pregnancy
Meniscus injury
Muscle rupture
Muscle strain
Postoperative ileus
Procedural pain

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

4
12
30
1
1
3
1

0.2
0.5
1.3
0.0
0.0
0.1
0.0

(0.0, 0.4)
(0.3, 0.9)
(0.9, 1.8)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)

90
1
2
3
1
9
1
5
1
1
20
2
4
1
3
1
1
1
1
6
4
1
1
3
1
1
2
1
6

3.8
0.0
0.1
0.1
0.0
0.4
0.0
0.2
0.0
0.0
0.8
0.1
0.2
0.0
0.1
0.0
0.0
0.0
0.0
0.3
0.2
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.3

(3.0, 4.7)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.2, 0.7)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.5, 1.3)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.1, 0.5)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

Radius fracture
Road traffic accident
Scapula fracture
SeromaSkin abrasion
Skin laceration
Spinal fracture
Subdural haematoma
Tendon injury
Tendon rupture
Thermal burn
Tooth fracture
Traumatic intracranial haemorrhage
Upper limb fracture
Wound
Wrist fracture

1
2
1
1
2
10
1
1
1
1
2
6
1
2
1
1

0.0
0.1
0.0
0.0
0.1
0.4
0.0
0.0
0.0
0.0
0.1
0.3
0.0
0.1
0.0
0.0

(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.2, 0.8)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

INVESTIGATIONS
Alanine aminotransferase increased
Antinuclear antibody positive
Aspartate aminotransferase increased
Blood cholesterol increased
Blood pressure increased
Blood testosterone decreased
Body temperature increased
C-reactive protein increased
Heart rate increased
SARS-CoV-2 antibody test positive
Troponin increased

107
2
1
2
3
6
2
91
1
1
1
1

4.5
0.1
0.0
0.1
0.1
0.3
0.1
3.8
0.0
0.0
0.0
0.0

(3.7, 5.4)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.1, 0.5)
(0.0, 0.3)
(3.1, 4.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

METABOLISM AND NUTRITION DISORDERS
Decreased appetite
Diabetes mellitus
Diabetes mellitus inadequate control
Dyslipidaemia
Glucose tolerance impaired
Gout
Hypercholesterolaemia

29
14
1
1
2
2
1
1

1.2
0.6
0.0
0.0
0.1
0.1
0.0
0.0

(0.8, 1.8)
(0.3, 1.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Hyperglycaemia
Insulin resistance
Lactic acidosis
Type 2 diabetes mellitus
Vitamin D deficiency
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia
Arthritis
Back pain
Bursitis
Flank pain
Foot deformity
Groin pain
Intervertebral disc protrusion
Joint range of motion decreased
Joint swelling
Limb discomfort
Mobility decreased
Muscle fatigue
Muscle spasms
Muscular weakness
Musculoskeletal chest pain
Musculoskeletal pain
Musculoskeletal stiffness
Myalgia
Neck pain
Osteoarthritis
Osteoporosis
Pain in extremity
Periarthritis
Plantar fasciitis
Rheumatoid arthritis
Rotator cuff syndrome
Sacroiliitis
Sjogren's syndrome
Synovial cyst

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

2
2
1
2
1

0.1
0.1
0.0
0.1
0.0

(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)

1245
149
3
32
1
2
1
1
2
2
1
1
1
2
1
4
1
1
12
925
11
9
1
154
1
3
1
2
1
1
1

52.3
6.3
0.1
1.3
0.0
0.1
0.0
0.0
0.1
0.1
0.0
0.0
0.0
0.1
0.0
0.2
0.0
0.0
0.5
38.9
0.5
0.4
0.0
6.5
0.0
0.1
0.0
0.1
0.0
0.0
0.0

(49.5, 55.3)(5.3, 7.4)
(0.0, 0.4)
(0.9, 1.9)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.3, 0.9)
(36.4, 41.5)(0.2, 0.8)
(0.2, 0.7)
(0.0, 0.2)
(5.5, 7.6)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Temporomandibular joint syndrome
Tendonitis
Trigger finger

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

1
1
1

0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL
CYSTS AND POLYPS)
Bladder neoplasm
Bowen's disease
Brain neoplasm
Breast cancer
Breast cancer stage II
Hepatic cancer
LipomaMeningioma
Neoplasm
Non-small cell lung cancer stage III
Rectal cancer
Seborrhoeic keratosis
Skin papilloma
Squamous cell carcinoma

13

0.5

(0.3, 0.9)

1
1
1
1
1
1
1
1
1
1
1
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NERVOUS SYSTEM DISORDERS
Amnesia
Arachnoid cyst
Balance disorder
Brachial plexopathy
Carpal tunnel syndrome
Cerebrovascular accident
Cervical radiculopathy
Cognitive disorderDisturbance in attention
Dizziness
Dysgeusia
Encephalopathy
Facial paralysis
Head discomfort
HeadacheHemiplegia

1201
1
1
2
1
1
4
1
1
4
47
2
1
3
1
1108
1

50.5
0.0
0.0
0.1
0.0
0.0
0.2
0.0
0.0
0.2
2.0
0.1
0.0
0.1
0.0
46.6
0.0

(47.7, 53.4)(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(1.5, 2.6)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(43.9, 49.4)(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Hyperaesthesia
Hypoaesthesia
Hypogeusia
Lethargy
Loss of consciousness
Mental impairment
Migraine
Migraine with aura
Nerve compression
Paraesthesia
Parosmia
Piriformis syndrome
Presyncope
Radiculopathy
Sciatica
SeizureSomnolence
Speech disorder
Syncope
Transient ischaemic attack
TremorVisual field defect
PSYCHIATRIC DISORDERS
Abnormal dreams
Alcohol withdrawal syndrome
Anxiety
Attention deficit hyperactivity disorder
Bipolar disorder
Completed suicide
Confusional state
Depression
Generalised anxiety disorder
Insomnia
Irritability
Major depression
Mental fatigue

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

2
2
1
9
1
2
6
1
1
14
1
1
1
1
1
1
13
1
4
2
2
1

0.1
0.1
0.0
0.4
0.0
0.1
0.3
0.0
0.0
0.6
0.0
0.0
0.0
0.0
0.0
0.0
0.5
0.0
0.2
0.1
0.1
0.0

(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.3, 1.0)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.3, 0.9)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)

43
1
1
9
3
1
1
2
3
1
12
2
1
1

1.8
0.0
0.0
0.4
0.1
0.0
0.0
0.1
0.1
0.0
0.5
0.1
0.0
0.0

(1.3, 2.4)
(0.0, 0.2)
(0.0, 0.2)
(0.2, 0.7)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.3, 0.9)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Mental status changes
Restlessness
Sleep disorder
Suicidal ideation
Suicide attempt
Thinking abnormal

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

1
2
2
1
1
1

0.0
0.1
0.1
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

RENAL AND URINARY DISORDERS
Acute kidney injury
Bladder neck obstruction
Chronic kidney disease
Dysuria
Haematuria
Hypertonic bladder
Nephrolithiasis
Pollakiuria
Urinary bladder polyp
Urinary hesitation
Urinary retention
Urinary tract obstruction

21
1
1
1
6
1
2
4
1
1
1
1
1

0.9
0.0
0.0
0.0
0.3
0.0
0.1
0.2
0.0
0.0
0.0
0.0
0.0

(0.5, 1.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Benign prostatic hyperplasia
Breast cyst
Breast discharge
Endometriosis
Metrorrhagia
Ovarian cyst
Pelvic pain
Sexual dysfunction
Testicular pain
Uterine haemorrhage
Vaginal lesion

12
3
1
1
1
2
1
1
1
1
1
1

0.5
0.1
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0

(0.3, 0.9)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Acute respiratory failure
AsthmaChronic obstructive pulmonary disease
Cough

37
2
1
1
3

1.6
0.1
0.0
0.0
0.1

(1.1, 2.1)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

Dyspnoea
Epistaxis
Immune-mediated pneumonitis
Nasal congestion
Nasal septum deviation
Oropharyngeal pain
Paranasal sinus discomfort
Pleuritic pain
Pulmonary embolism
Rhinitis allergic
Rhinorrhoea
Sinus congestion
Upper respiratory tract congestion
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Acne
Actinic keratosis
Alopecia
Angioedema
Cold sweat
Dermatitis
Dermatitis contact
Dry skin
Ecchymosis
Erythema
Erythema nodosum
Hyperhidrosis
Ingrowing nailLichen sclerosus
Night sweats
Petechiae
Pruritus
Rash
Rash erythematous
Rash pruritic
Rash vesicular
Skin lesion

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

2
3
1
5
1
1
1
1
4
4
6
1
1

0.1
0.1
0.0
0.2
0.0
0.0
0.0
0.0
0.2
0.2
0.3
0.0
0.0

(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.4)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)

85
1
3
2
1
1
2
6
1
3
2
1
15
3
1
7
1
6
16
2
1
1
4

3.6
0.0
0.1
0.1
0.0
0.0
0.1
0.3
0.0
0.1
0.1
0.0
0.6
0.1
0.0
0.3
0.0
0.3
0.7
0.1
0.0
0.0
0.2

(2.9, 4.4)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.3)
(0.0, 0.2)
(0.4, 1.0)
(0.0, 0.4)
(0.0, 0.2)
(0.1, 0.6)
(0.0, 0.2)
(0.1, 0.5)
(0.4, 1.1)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 15. Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff
Date (13MAR2021), by System Organ Class and Preferred Term – OpenLabel Follow-up Period – Subjects Who Originally Received Placebo andThen Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Skin ulcer
Urticaria

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

1
7

0.0
0.3

(0.0, 0.2)
(0.1, 0.6)

SURGICAL AND MEDICAL PROCEDURES
Blepharoplasty
Chondroplasty
Finger repair operation
Hysterectomy
Injection
Spinal fusion surgery
Tooth extraction

9
1
1
1
2
1
1
2

0.4
0.0
0.0
0.0
0.1
0.0
0.0
0.1

(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)

VASCULAR DISORDERS
Aortic aneurysm
Aortic arteriosclerosis
Aortic stenosis
Blood pressure fluctuation
Deep vein thrombosis
Flushing
Haematoma
Hot flush
Hypertension
Hypotension
Peripheral coldness
Thrombosis
Venous thrombosis limb

45
1
1
1
1
3
5
2
2
25
1
1
1
1

1.9
0.0
0.0
0.0
0.0
0.1
0.2
0.1
0.1
1.1
0.0
0.0
0.0
0.0

(1.4, 2.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)
(0.1, 0.5)
(0.0, 0.3)
(0.0, 0.3)
(0.7, 1.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

Note: Dose 3 = First dose of BNT162b2 (30 μg).
Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 3 to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(17:36)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 exp age p3x saf

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BNT162b2
2.7.4 Summary of Clinical Safety

2.7.4.2.4.2.5.2.2. Related Adverse Events by System Organ Class and Preferred Term:
Open-Label Follow-Up Period – Original Placebo Participants Who Then Received
BNT162b2 (Phase 3, Study C4591001, Analysis of Adverse Events)
From vaccination with BNT162b2 to the data cutoff date for placebo participants, the IR of
AEs assessed as related by the investigator during the open-label follow-up period was
189.5 per 100 PY (Table 14). The IRs of related AEs were highest for reactogenicity eventsand in the SOC of general disorders and administration site conditions (4147 [174.3 per
100 PY]) for the following PTs:injection site pain (2938 [123.5 per 100 PY])
pyrexia (905 [38.0 per 100 PY])
fatigue (1373 [57.7 per 100 PY])
chills (993 [41.7 per 100 PY])

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

2.7.4.2.4.2.5.2.3. Immediate Adverse Events: Open-Label Follow-Up Period – Original
Placebo Participants Who Then Received BNT162b2 (Phase 3, Study C4591001,
Analysis of Adverse Events)
After vaccination with BNT162b2 (Dose 3/4), placebo participants who received BNT162b2
with immediate AEs were low in frequency (0.6%). Most immediate AEs after BNT162b2
doses were in the SOC of general disorders and administration site conditions, primarily
injection site reactions, with injection site pain (0.4%) most frequently reported.
Other immediate AEs were reported in the following, and were assessed by the investigatoras related to study intervention:One participant in the younger age group reported 2 immediate AEs of oedema mouth
and tongue edema (both mild in severity) after Dose 4; both AEs were assessed by theinvestigator as related to study intervention. The AE of tongue oedema resolved the same
day and the AE of oedema mouth resolved the following day.



One participant in the younger age group reported an immediate AE of hypoaesthesia
oral (mild) after Dose 3 and resolved the same day.



One participant in the younger age group reported 3 immediate AEs of swelling face,
allergy to vaccine, and flushing after Dose 3, which were all were moderate in severity.
All 3 AEs resolved the following day. The participant also reported nausea and urticaria(hives abdomen) (both mild in severity) on the same day but were not immediate. The AEof nausea resolved the same day and the AE of urticaria resolved the following day.
These 2 AEs were also assessed by the investigator as related to study intervention.

One participant in the older age group reported an immediate AE of urticaria (hive onback of neck; moderate in severity) after Dose 4 and is ongoing at the time of the data
cutoff date.

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2.7.4.2.4.2.5.2.4. Severe or Life-Threatening Adverse Events: Open-Label Follow-Up
Period – Original Placebo Participants Who Then Received BNT162b2 (Phase 3, Study
C4591001, Analysis of Adverse Events)
Severe Adverse Events

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

From Dose 3 (first Dose of BNT162b2) to the data cutoff date, the severe AE IR was 6.0 per
100 PY in original placebo participants. Severe AEs included:One participant in the younger age group reported a severe AE of hypersensitivity on 13
days after Dose 3, which resolved the following day and was assessed by the investigator
as not related to study intervention.

One participant in the older age group reported a severe SAE of COVID-19 pneumonia 8days after Dose 3, which resolved 4 days later and was assessed by the investigator as not
related to study intervention.

One participant in the older age group reported a severe SAE of cerebrovascular accident
16 days after Dose 4, which was assessed by the investigator as not related to study
intervention and ongoing at the time of the data cutoff date.

One participant in the younger age group reported a severe SAE of pulmonary embolism
5 days after Dose 4, which resolved the following day and was assessed by theinvestigator as not related to study intervention.

One participant in the older age group reported 1 severe SAE each of pulmonary
embolism and thrombosis (occlusive thrombus in the right calf) 2 days after Dose 3. Bothevents resolved the following day, and both were assessed by the investigator as not
related to study intervention.

One participant in the younger age group reported 2 AEs of urticaria (moderate andsevere) at 3 and 4 days after Dose 3, respectively. The moderate AE of urticaria(intermittent generalized) resolved the same day. The severe AE of urticaria (left arm)
resolved 8 days later. Both events were assessed by the investigator as related to study
intervention.

Life-Threatening Adverse EventsThe IR for original placebo participants who had at least 1 life-threatening AE from Dose 3
to the data cutoff date was 0.5 per 100 PY. The following life-threatening events werereported and with the exception of anaphylactoid reaction, all were considered unrelated tovaccine as assessed by the investigator.


A Grade 4 life-threatening SAE of cardio-respiratory arrest was reported in one
participant in the older age group. The event occurred 25 days after Dose 3 and theoutcome was fatal.

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2.7.4 Summary of Clinical Safety

One participant in the younger age group had a Grade 4 life-threatening SAE ofgastrointestinal necrosis 29 days after Dose 4. The outcome was not recovered/not
resolved at the time of this report.

One participant in the younger age group had a Grade 4 life-threatening SAE of
pulmonary embolism and a Grade 4 life-threatening SAE of deep vein thrombosis. Bothevents of pulmonary embolism and deep vein thrombosis occurred 11 days after Dose 4
and the outcome for both events was recovering/resolving.



A Grade 4 life-threatening SAE of anaphylactoid reaction was reported in one participant
in the younger age group 2 days after Dose 3. The outcome was recovered/resolved andthe event was considered related to vaccine. This participant is also discussed under
Section 2.7.4.2.4.3.4.1.1.

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2.7.4.2.4.2.6. Original Placebo Participants, had COVID-19 Occurrence After Dose 1,
and Then Received BNT162b2: Open-Label Follow-Up Period (Phase 3, Study
C4591001)
2.7.4.2.4.2.6.1. Summary of Adverse Events: Original Placebo Participants, had
COVID-19 Occurrence After Dose 1, and Then Received BNT162b2: Open-Label
Follow-Up Period (Phase 3, Study C4591001)
There were 853 original placebo participants who developed COVID-19 and subsequently
were vaccinated with BNT162b2. For original placebo participants who had COVID-19
occurrence after Dose 1 and then received BNT162b2, IRs for any AE and at least 1 related
AE from Dose 3 (first dose of BNT162b2 30 µg) were 256.8 per 100 PY and 240.9 per 100
PY, respectively. IRs of severe AEs, SAEs, and AEs leading to withdrawal were 4.6 per 100
PY, 3.4 per 100 PY, and 3.4 per 100 PY. The IR for discontinuations because of related AEs
was 3.4 per 100 PY, and no participants died.
IRs for SAEs were similar for the placebo participants who developed COVID-19 andsubsequently were vaccinated with BNT162b2 (3.4 per 100 PY; 95% CI: 0.7, 10.0) andparticipants originally randomized to BNT162b2 (3.2 per 100 PY; 95% CI: 2.8, 3.6)
(Table 7), respectively. None of the SAEs in the original placebo participants who developed
COVID-19 and subsequently were vaccinated with BNT162b2 were related to BNT162b2.
There were 3 participants with AEs leading to withdrawal that were assessed as related to
BNT162b2: 1 participant with an AE of allergy to vaccine, 1 participant with an AE of pain,
and 1 participant with 5 AEs (chills, injection site pain, myalgia, headache, and diarrhea). No
deaths were reported in placebo participants who developed COVID-19 and subsequently
were vaccinated with BNT162b2.
While the exposure time between the placebo participants who developed COVID-19 andsubsequently were vaccinated with BNT162b2 is small (0.9) compared to the exposure time
for the blinded placebo controlled period (83.4) (Table 7), direct comparisons must be
interpreted with caution, the rate of SAE were similar between the groups (3.4 per 100 PY vs
3.2 per 100 PY, respectively).

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2.7.4 Summary of Clinical Safety

2.7.4.2.4.2.6.2. Analysis of Adverse Events: Original Placebo Participants, had COVID19 Occurrence After Dose 1, and Then Received BNT162b2: Open-Label Follow-Up
Period (Phase 3, Study C4591001)
For original placebo participants who had COVID-19 occurrence after Dose 1 and thenreceived BNT162b2, the IR for at least 1 AE was 256.8 per 100 PY.
Most AEs reported from Dose 3 (the first dose of BNT162b2) to the data cutoff date were in
SOCs with reactogenicity events.


general disorders and administration site conditions (236.3 per 100 PY)
musculoskeletal and connective tissue disorders (47.9 per 100 PY)
nervous system disorders (66.2 per 100 PY)
gastrointestinal disorders (17.1 per 100 PY).

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2.7.4.2.4.3. Deaths, Serious Adverse Events, Safety-Related Participant Withdrawals,
and Other Significant Adverse Events (Phase 3, Study C4591001)
Full details and outputs regarding deaths, SAEs, safety-related participant withdrawals, andother significant AEs for Phase 3 of Study C4591001 are in Module 5.3.5.1 C4591001
6-Month Update CSR Section 12.2.4.
2.7.4.2.4.3.1. Deaths (Phase 3, Study C4591001)
There were 15 deaths in the BNT162b2 group and 14 deaths in the placebo group from
Dose 1 to the unblinding date during the blinded placebo-controlled follow-up period(Table 16). None of these deaths were assessed by the investigator as related to study
intervention.

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Table 16. Incidence Rates of Deaths From Dose 1 to Unblinding Date – Blinded
Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)nc
Deaths
Cause of deathf
Acute respiratory failure
Aortic rupture
Arteriosclerosis
Biliary cancer metastatic
COVID-19
COVID-19 pneumonia
Cardiac arrest
Cardiac failure congestive
Cardio-respiratory arrest
Chronic obstructive pulmonary disease
Death
Dementia
Emphysematous cholecystitis
Haemorrhagic stroke
Hypertensive heart disease
Lung cancer metastatic
Metastases to liver
Missing
Multiple organ dysfunction syndrome
Myocardial infarction
Overdose
Pneumonia
Sepsis
Septic shock
Shigella sepsis
Unevaluable event

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR (/100 PY)d(95% CIe)nc

Placebo(Na=21921, TEb=82.2)
IR (/100 PY)d(95% CIe)15

0.2(0.1, 0.3)

14

0.2

(0.1, 0.3)

0
0
2
0
0
1
4
1
1
1
0
0
1
0
1
1
0
0
0
0
0
0
1
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

1
1
0
1
2
0
1
0
1
0
1
1
0
1
0
0
1
1
2
2
1
2
0
0
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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2.7.4 Summary of Clinical Safety

Table 16. Incidence Rates of Deaths From Dose 1 to Unblinding Date – Blinded
Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population
Vaccine Group (as Administered)nc

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
IR (/100 PY)d(95% CIe)nc

Placebo(Na=21921, TEb=82.2)
IR (/100 PY)d(95% CIe)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified cause of death.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f. Multiple causes of death can be reported for each subject.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: dd Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/addd s001 p3 saf

From the unblinding date to the data cutoff date of the open-label follow-up period, there
were 3 deaths in original BNT162b2 participants (all in the older age group, one each due toroad traffic accident, lung metastases, and myocardial infarction) and 2 deaths in originalplacebo participants who then received BNT162b2 (all in the older age group, one each due
to cardiorespiratory arrest or completed suicide). None of these deaths were assessed by theinvestigator as related to study intervention.
Among participants with confirmed stable HIV disease, 2 deaths were reported as of thecutoff date, and none of these deaths were assessed by the investigator as related to study
intervention:
One female participant in the younger age group died due to COVID-19 pneumonia
reported 75 days after receiving Dose 2 of placebo. This participant was diagnosed
based on a local COVID-19 test that could not be confirmed as protocol-approved
and was not confirmed by a test result from the central laboratory. Therefore, thisparticipant was not included in efficacy analyses.

One female participant in the older age group died due to a road traffic accident
occurring 73 days after receiving Dose 2.

2.7.4.2.4.3.1.1. Death Narratives (Phase 3, Study C4591001)
Narratives for the participants who died through the data cutoff date (13 March 2021) areprovided (see Section 2.7.4.2.4.4).

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2.7.4.2.4.3.2. Serious Adverse Events (Phase 3, Study C4591001)
Details and outputs regarding serious adverse events for Phase 3 of Study C4591001 are in
Module 5.3.5.1 C4591001 6-Month Update CSR Section 12.2.4.2.
2.7.4.2.4.3.2.1. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to 1 Month
After Dose 2 (Phase 3, Study C4591001, Serious Adverse Events)
From Dose 1 to 1 month after Dose 2 the proportions of participants who reported at least 1
SAE was similar in the BNT162b2 group (0.6%) and in the placebo group (0.5%) (Table 17).
The numbers of participants who reported at least 1 SAE were lower in the younger age
group (52 [0.4%] and 49 [0.4%] for the BNT162b2 and placebo groups, respectively) than in
the older age groups was (75 [0.8%] and 67 [0.8%] for the BNT162b2 and placebo groups,
respectively) similar.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)Three of the SAEs in the BNT162b2 group and none in the placebo group were assessed by
the investigator as related to study intervention (Table 5).
In the BNT162b2 group, there were 2 participants in the younger age group (previously
reported in the final analysis interim C4591001 CSR dated 03 December 2020) and 1
participant in the older age group with an SAE each assessed by the investigator as related to
study intervention:One participant in the younger age group had an SAE of lymphadenopathy (rightaxilla) 13 days after Dose 1 which lasted 66 days and resolved. The participant was a
48-year-old woman with a relevant medical history of eczema and topical crisaborole
use who was administered BNT162b2 vaccine in the left deltoid and had rightaxillary pain and lymphadenopathy. She had no injuries to the right arm, no fever,and no history of a similar incident. Her WBC was normal with a normal lymphocyte
count and a right axilla ultrasound showed 4 enlarged lymph nodes (largest 2.5 × 1.1
× 2.4 cm). A biopsy was performed and was reported to be normal and withoutmarkers for lymphoma or other cancer. A follow-up visit with oncology (and possible
repeat ultrasound) was planned for 3 months’ time.

One participant in the younger age group had an SAE of shoulder injury related tovaccine administration (SIRVA, erroneously administered into or near the shoulder
joint capsule) after Dose 2, which lasted 153 days and resolved.



One participant in the older age group with a past medical history significant for AV
block with pacemaker, sinus node dysfunction, atrial fibrillation, and supraventriculartachycardia had an SAE of ventricular arrhythmia that occurred 1 day after Dose 2
and lasted for 8 days and resolved.

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Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Any event127 (0.6)(0.5, 0.7)

116 (0.5)(0.4, 0.6)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymphadenopathy
Neutropenia
Thrombocytopenia

1 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Atrial fibrillation
Acute myocardial infarction
Acute coronary syndromeCoronary artery disease
Myocardial infarction
Aortic valve incompetence
Bradycardia
Cardiac arrest
Cardiac failure congestive
Acute left ventricular failure
Angina pectoris
Angina unstable
Arrhythmia supraventricular
Arteriospasm coronary
Cardiac failure acuteCoronary artery dissection
Coronary artery occlusion
Junctional ectopic tachycardia
Myocardial ischaemia
Pericarditis
Tachyarrhythmia
Tachycardia
Ventricular arrhythmia

20 (0.1)
2 (0.0)3 (0.0)1 (0.0)2 (0.0)001 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)001 (0.0)001 (0.0)1 (0.0)001 (0.0)(0.1, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

21 (0.1)
4 (0.0)1 (0.0)2 (0.0)1 (0.0)3 (0.0)2 (0.0)1 (0.0)01 (0.0)0000
1 (0.0)1 (0.0)01 (0.0)1 (0.0)001 (0.0)1 (0.0)0(0.1, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Congenital bladder neck obstruction
Heart disease congenital

1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
Vertigo

2 (0.0)2 (0.0)(0.0, 0.0)
(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

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Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

EYE DISORDERS
Choroidal neovascularisation
Diplopia
Retinal artery occlusion
Visual impairment

2 (0.0)1 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)001 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GASTROINTESTINAL DISORDERS
Small intestinal obstruction
Pancreatitis acute
Abdominal adhesions
Abdominal pain
Abdominal pain upper
ColitisDiarrhoea
Diverticular perforation
Gastrointestinal haemorrhage
Gastrointestinal mucosa hyperaemia
Incarcerated inguinal hernia
Inguinal hernia
Intestinal obstruction
Obstructive pancreatitis
Oesophageal food impaction
Oesophageal varices haemorrhage
Pancreatitis
Salivary gland calculus
Umbilical hernia
Volvulus

9 (0.0)2 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)01 (0.0)001 (0.0)001 (0.0)00
0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

12 (0.1)
1 (0.0)2 (0.0)001 (0.0)001 (0.0)01 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONS
Non-cardiac chest pain
Chest pain
Death
Influenza like illness
Shoulder injury related to vaccine administration
Vascular stent occlusion

4 (0.0)(0.0, 0.0)

3 (0.0)(0.0, 0.0)

2 (0.0)000
1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)01 (0.0)1 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

HEPATOBILIARY DISORDERS
Cholecystitis acute
Cholelithiasis

6 (0.0)1 (0.0)3 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)2 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Bile duct stone
Cholecystitis

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Anaphylactic reaction
Anaphylactic shock
Drug hypersensitivity

2 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INFECTIONS AND INFESTATIONSAppendicitis
Pneumonia
Cellulitis
Urinary tract infection
Appendicitis perforated
COVID-19
Diverticulitis
Peritonsillar abscess
Postoperative wound infection
Pyelonephritis
Abdominal abscess
Abscess
Abscess intestinal
Anal abscess
Bacterial sepsis
Brain abscessComplicated appendicitis
EmpyemaMeningitis bacterial
Osteomyelitis
Peritoneal abscess
Peritonitis
Pyelonephritis acute
Shigella sepsis
Staphylococcal infection
Subacute endocarditis
Subcutaneous abscess
Suspected COVID-19
Upper respiratory tract infection
Urosepsis

27 (0.1)
7 (0.0)2 (0.0)2 (0.0)3 (0.0)1 (0.0)02 (0.0)1 (0.0)2 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)001 (0.0)001 (0.0)01 (0.0)1 (0.0)1 (0.0)001 (0.0)00(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

21 (0.1)
3 (0.0)4 (0.0)2 (0.0)1 (0.0)1 (0.0)2 (0.0)01 (0.0)001 (0.0)0000
1 (0.0)1 (0.0)01 (0.0)1 (0.0)01 (0.0)000
1 (0.0)1 (0.0)01 (0.0)1 (0.0)(0.1, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Overdose
Facial bones fracture
Road traffic accident
Alcohol poisoning
Cervical vertebral fracture
Colon injury
Fall
Femur fracture
Flail chest
Foot fracture
Forearm fracture
Head injury
Hip fracture
Humerus fracture
Lower limb fracture
Multiple injuries
Procedural haemorrhage
Rib fracture
Spinal column injury
Spinal cord injury cervical
Subdural haematoma
Toxicity to various agents
Traumatic haemothorax
Traumatic intracranial haemorrhage
Ulna fracture

8 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)
0
0
0
0
0
0
0
1 (0.0)000
000
1 (0.0)000
1 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

15 (0.1)
1 (0.0)01 (0.0)001 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INVESTIGATIONS
Blood glucose abnormal
Cardiac stress test abnormal
Hepatic enzyme increased

1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

METABOLISM AND NUTRITION DISORDERS
Diabetic ketoacidosis
Fluid retention
Hypoglycaemia
Hypokalaemia

2 (0.0)1 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)001 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

MUSCULOSKELETAL AND CONNECTIVE TISSUEDISORDERS

7 (0.0)(0.0, 0.1)

5 (0.0)(0.0, 0.1)

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System Organ Class
Preferred Term

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Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

3 (0.0)2 (0.0)01 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)1 (0.0)1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED(INCL CYSTS AND POLYPS)
Prostate cancer
Malignant melanoma
Uterine leiomyoma
Adenocarcinoma gastric
Adenocarcinoma pancreas
Adrenal gland cancer
Biliary cancer metastatic
Breast cancer
Chronic myeloid leukaemia
Intraductal proliferative breast lesion
Invasive ductal breast carcinoma
Leydig cell tumour of the testis
Meningioma
Metastases to central nervous system
Metastases to liver
Oropharyngeal squamous cell carcinoma
Pancreatic carcinoma
Penile neoplasm
Prostate cancer metastatic
Thyroid cancer

13 (0.1)(0.0, 0.1)

10 (0.0)(0.0, 0.1)

2 (0.0)1 (0.0)01 (0.0)1 (0.0)1 (0.0)00000
1 (0.0)1 (0.0)1 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)2 (0.0)000
1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)000
1 (0.0)01 (0.0)00
0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

NERVOUS SYSTEM DISORDERS
Subarachnoid haemorrhage
Syncope
Cerebrovascular accident
Ischaemic stroke
Transient ischaemic attack
Amnesia
Amyotrophic lateral sclerosis
Cerebral infarction

14 (0.1)
4 (0.0)1 (0.0)3 (0.0)1 (0.0)2 (0.0)00
0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

15 (0.1)
1 (0.0)4 (0.0)01 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)Intervertebral disc protrusion
Osteoarthritis
Arthralgia
Back pain
Muscular weakness
Osteochondritis

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)00001 (0.0)001 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)1 (0.0)1 (0.0)01 (0.0)1 (0.0)00(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)000(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

PSYCHIATRIC DISORDERS
Suicidal ideation
Bipolar disorder
Depression suicidal
Disorientation
Mental disorder
Psychotic disorder
Suicide attempt

3 (0.0)000
1 (0.0)1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

5 (0.0)2 (0.0)1 (0.0)1 (0.0)000
1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

RENAL AND URINARY DISORDERS
Nephrolithiasis
Acute kidney injury
Renal colic
Subcapsular renal haematoma
Urinary bladder polyp5 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)0000
1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Breast hyperplasia
Ovarian cyst
Ovarian mass
Uterine prolapse

2 (0.0)1 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)001 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Pulmonary embolism
Acute respiratory failure
Pneumonia aspiration
Chronic obstructive pulmonary disease

7 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

6 (0.0)3 (0.0)01 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Cervicogenic headache
Dizziness
Haemorrhagic stroke
Hemiplegic migraine
Idiopathic intracranial hypertension
Paraesthesia
Spinal cord compression
Transient global amnesia
Uraemic encephalopathy
PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS
Abortion spontaneous
Abortion spontaneous incomplete

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 17. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

HypoxiaInterstitial lung disease
Pneumonitis
Pneumothorax
Pulmonary mass
Respiratory arrest

0
1 (0.0)1 (0.0)00
0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)001 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS
Deep vein thrombosis
Hypertension
Orthostatic hypotension
Aortic stenosis
Arteriosclerosis
Hypertensive crisis
Hypertensive urgency

7 (0.0)2 (0.0)2 (0.0)001 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

5 (0.0)2 (0.0)02 (0.0)1 (0.0)00
0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:10)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s130_ser_all_pd2_p3_saf

2.7.4.2.4.3.2.1.1. Participants with Confirmed Stable HIV Disease: Blinded Follow-Up
Period From Dose 1 to 1 Month After Dose 2 (Phase 3, Study C4591001, Serious
Adverse Events)
No participants with confirmed stable HIV disease reported an SAE from Dose 1 to 1 monthafter Dose 2.
2.7.4.2.4.3.2.2. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to the
Unblinding Date (Phase 3, Study C4591001, Serious Adverse Events)
From Dose 1 to the unblinding date, IRs of at least 1 SAE were similar in the BNT162b2
group (3.2 per 100 PY) and in the placebo group (3.3 per 100 PY) (Table 18). The IR was
lower in the younger age groups (2.1 per 100 PY and 2.4 per 100 PY for the BNT162b2 andCONFIDENTIAL
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2.7.4 Summary of Clinical Safety

placebo groups, respectively) than in the older age groups (4.9 per 100 PY and 4.6 per 100
PY for the BNT162b2 and placebo groups respectively).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Four of the SAEs in the BNT162b2 group and 1 in the placebo group were assessed by theinvestigator as related to study intervention. In addition to the 3 related SAEs in the
BNT162b2 group described in Section 2.7.4.2.4.3.2.1, there were 2 related SAEs that
occurred from Dose 1 to the unblinding date:One participant in the BNT162b2 younger age group with a medical history
significant for occipital neuralgia, and migraines had an SAE of paraesthesia (rightleg) 47 days after Dose 2 which was recovering/resolving at the data cutoff date.

One participant in the placebo younger age group had an SAE of psoriatic arthropathy
38 days after Dose 2 which was continuing at the data cutoff date.

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)(/100 PY)dAny event

268

3.2

(2.8, 3.6)

268

3.3

(2.9, 3.7)

BLOOD AND LYMPHATIC SYSTEMDISORDERS
Anaemia
Lymphadenopathy
Microcytic anaemia
Neutropenia
Thrombocytopenia

1

0.0(0.0, 0.1)

4

0.0

(0.0, 0.1)

0
1
0
0
0

0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1
0
1
1
2

0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

CARDIAC DISORDERS
Acute coronary syndrome
Acute left ventricular failure
Acute myocardial infarction
Angina pectoris
Angina unstable
Aortic valve incompetence
Arrhythmia supraventricular
Arteriosclerosis coronary artery
Arteriospasm coronary
Atrial fibrillation
Atrioventricular block complete
Bradycardia

42
1
1
6
3
2
0
1
0
0
5
1
1

0.5
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.4, 0.7)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

39
3
0
3
0
1
2
0
1
1
9
0
1

0.5
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0

(0.3, 0.6)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.2)
(0.0, 0.0)
(0.0, 0.1)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)(/100 PY)dCONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Cardiac arrest
Cardiac failure acute
Cardiac failure congestive
Cardio-respiratory arrest
Coronary artery disease
Coronary artery dissection
Coronary artery occlusion
Hypertensive heart disease
Junctional ectopic tachycardia
Myocardial infarction
Myocardial ischaemia
Pericarditis
Tachyarrhythmia
Tachycardia
Ventricular arrhythmia
Ventricular tachycardia

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

6
0
3
1
3
1
0
1
0
4
1
1
0
0
1
1

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

2
1
1
1
3
0
1
0
1
7
0
0
1
1
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

CONGENITAL, FAMILIAL AND GENETICDISORDERSCongenital bladder neck obstruction
Congenital ureteropelvic junction obstruction
Heart disease congenital1

0.0(0.0, 0.1)

2

0.0

(0.0, 0.1)

0
0
1

0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

1
1
0

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
Vertigo

2
2

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

1
1

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

EYE DISORDERS
Blindness unilateral
Choroidal neovascularisation
Diplopia
Eye haemorrhage
Ophthalmic vein thrombosis
Retinal artery occlusion
Visual impairment

5
1
1
1
0
1
0
1

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

3
0
0
0
1
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

GASTROINTESTINAL DISORDERS
Abdominal adhesions
Abdominal hernia
Abdominal pain
Abdominal pain upper
ColitisColitis ischaemic

23
1
1
1
0
2
0

0.3
0.0
0.0
0.0
0.0
0.0
0.0

(0.2, 0.4)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

21
0
0
0
1
0
1

0.3
0.0
0.0
0.0
0.0
0.0
0.0

(0.2, 0.4)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Constipation
Diarrhoea
Diverticular perforation
Diverticulum intestinal
Duodenal obstruction
Enterocolitis
Food poisoning
Gastritis
Gastrointestinal haemorrhage
Gastrointestinal mucosa hyperaemia
Haemorrhoids
Hiatus hernia
Ileus
Impaired gastric emptying
Incarcerated inguinal hernia
Inguinal hernia
Intestinal obstruction
Intestinal perforation
Intestinal strangulation
Large intestine perforation
Obstructive pancreatitis
Oesophageal food impaction
Oesophageal varices haemorrhage
Pancreatic cyst
Pancreatitis
Pancreatitis acute
Retroperitoneal haematoma
Salivary gland calculus
Small intestinal obstruction
Umbilical hernia
Volvulus

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
1
0
0
1
1
1
2
2
0
1
0
0
1
1
0
1
1
1
0
1
0
0
0
1
1
0
0
4
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
0
1
1
0
0
0
0
1
1
0
1
1
0
0
1
1
0
0
1
0
1
1
1
1
3
1
1
2
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

GENERAL DISORDERS AND ADMINISTRATION 10
SITE CONDITIONSAsthenia
1
Chest pain
3
Death
0
Drug withdrawal syndrome
1
Influenza like illness
0Multiple organ dysfunction syndrome
00.1(0.1, 0.2)

4

0.0

(0.0, 0.1)

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

0
1
1
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Non-cardiac chest pain
Shoulder injury related to vaccine administration
Sudden cardiac death
Vascular stent occlusion

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

3
1
1
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
0
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

HEPATOBILIARY DISORDERS
Bile duct stone
Biliary colic
Cholecystitis
Cholecystitis acute
Cholecystitis chronic
Cholelithiasis
Hepatocellular injury

12
2
2
1
4
0
5
0

0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.0

(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

7
0
0
1
3
1
1
1

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

IMMUNE SYSTEM DISORDERS
Anaphylactic reaction
Anaphylactic shock
Drug hypersensitivity

2
1
0
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

1
0
1
0

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

INFECTIONS AND INFESTATIONS
Abdominal abscess
Abscess
Abscess intestinal
Anal abscess
Appendicitis
Appendicitis perforated
Arthritis bacterial
Bacterial sepsis
Brain abscess
COVID-19
COVID-19 pneumonia
Cellulitis
Complicated appendicitis
Device related infection
Diabetic foot infection
Diverticulitis
Emphysematous cholecystitis
EmpyemaEscherichia urinary tract infection
Extradural abscessGangrene

50
0
1
1
1
14
1
1
1
0
0
1
3
0
1
0
4
1
1
1
0
1

0.6
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.4, 0.8)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

57
1
0
0
0
9
1
0
0
1
13
1
2
2
0
1
1
0
0
0
1
0

0.7
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.5, 0.9)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Gastroenteritis
Meningitis bacterial
Osteomyelitis
Penile infection
Peritoneal abscess
Peritonitis
Peritonsillar abscess
Pneumonia
Post procedural infection
Postoperative wound infection
Pyelonephritis
Pyelonephritis acute
Renal abscessRespiratory tract infection viral
Sepsis
Septic shock
Shigella sepsis
Staphylococcal infection
Staphylococcal sepsis
Subacute endocarditis
Subcutaneous abscess
Suspected COVID-19
Tooth infection
Upper respiratory tract infection
Urinary tract infection
Urosepsis
INJURY, POISONING AND PROCEDURALCOMPLICATIONS
Alcohol poisoning
Ankle fracture
Brain contusion
Cervical vertebral fracture
Colon injury
Concussion
Craniocerebral injury
Delayed recovery from anaesthesia
Facial bones fracture
Fall
Femur fracture

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
0
0
1
1
1
1
4
0
2
3
1
0
1
1
1
1
1
0
0
0
1
0
0
3
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

1
1
1
0
0
1
1
8
1
1
1
0
1
0
1
1
0
0
1
1
1
0
1
2
5
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

19

0.2

(0.1, 0.4)

26

0.3

(0.2, 0.5)

1
2
0
1
0
0
1
0
2
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

0
0
1
0
1
1
1
1
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

CONFIDENTIAL
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Flail chest
Foot fracture
Forearm fracture
Head injury
Hip fracture
Humerus fracture
Ligament rupture
Lower limb fracture
Lumbar vertebral fracture
Meniscus injury
Multiple injuries
Overdose
Patella fracture
Pelvic fracture
Post procedural haematoma
Post-traumatic pain
Procedural haemorrhage
Radius fracture
Rib fracture
Road traffic accident
Spinal column injury
Spinal cord injury cervical
Subdural haematoma
Tibia fracture
Toxicity to various agents
Traumatic haemothorax
Traumatic intracranial haemorrhage
Ulna fracture
Upper limb fracture
Wrist fracture

0
0
0
1
1
0
0
0
1
0
0
3
1
1
0
0
0
0
0
2
0
1
0
1
0
0
1
0
1
2

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

1
2
1
1
1
2
1
2
0
1
1
1
0
0
1
1
1
1
1
3
1
0
1
0
1
1
0
1
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

INVESTIGATIONS
Blood glucose abnormal
Blood pressure increased
Cardiac stress test abnormal
Hepatic enzyme increased
Red blood cell morphology abnormal

1
0
0
1
0
0

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

4
1
1
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

METABOLISM AND NUTRITION DISORDERS
Diabetes mellitus inadequate control

4
0

0.0
0.0

(0.0, 0.1)
(0.0, 0.0)

10
1

0.1
0.0

(0.1, 0.2)
(0.0, 0.1)

CONFIDENTIAL
Page 234
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Diabetic ketoacidosis
Fluid retention
Hyperglycaemia
Hypoglycaemia
Hypokalaemia
Hyponatraemia
Type 2 diabetes mellitus

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
1
0
1
1
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
0
2
2
1
1
2

0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

MUSCULOSKELETAL AND CONNECTIVE
TISSUE DISORDERS
Arthralgia
Arthritis
Back pain
Intervertebral disc compression
Intervertebral disc degeneration
Intervertebral disc protrusion
Muscular weakness
Osteoarthritis
Osteochondritis
Psoriatic arthropathy
Spondylolisthesis

13

0.2

(0.1, 0.3)

11

0.1

(0.1, 0.2)

0
1
1
1
1
3
0
4
1
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

2
0
0
0
1
2
1
3
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS)
Acute myeloid leukaemia
Adenocarcinoma gastric
Adenocarcinoma of colon
Adenocarcinoma pancreas
Adrenal gland cancer
B-cell lymphoma
Benign hydatidiform mole
Biliary cancer metastatic
Bladder cancer
Borderline serous tumour of ovary
Breast cancer
Breast cancer in situ
Breast cancer stage I
Carcinoid tumour of the stomach
Chronic myeloid leukaemia
Clear cell renal cell carcinoma
Colon adenoma

39

0.5

(0.3, 0.6)

35

0.4

(0.3, 0.6)

1
1
1
2
1
0
1
0
1
1
2
1
0
1
0
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

0
0
0
0
0
1
0
1
1
0
4
0
1
0
1
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

CONFIDENTIAL
Page 235
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Gallbladder cancer stage II
Gastric cancer
Intraductal proliferative breast lesion
Invasive ductal breast carcinoma
Leydig cell tumour of the testis
LipomaLobular breast carcinoma in situ
Lung adenocarcinoma
Lung cancer metastatic
Lymphoma
Malignant melanoma
Meningioma
Metastases to central nervous system
Metastases to liver
Metastases to lymph nodes
Non-Hodgkin's lymphoma recurrent
Non-small cell lung cancer stage IV
Oropharyngeal cancer recurrent
Oropharyngeal squamous cell carcinoma
Pancreatic carcinoma
Papillary serous endometrial carcinoma
Papillary thyroid cancer
Penile neoplasm
Plasma cell myeloma
Polycythaemia vera
Prostate cancer
Prostate cancer metastatic
Skin cancer
Squamous cell carcinoma
Squamous cell carcinoma of head and neck
Teratoma
Thyroid cancer
Tonsil cancer
Transitional cell carcinoma
Uterine cancer
Uterine leiomyoma
NERVOUS SYSTEM DISORDERS
Amnesia

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
1
0
2
1
1
0
0
1
1
1
1
1
0
0
0
1
0
1
0
0
0
1
1
0
3
1
1
1
0
0
1
1
2
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

0
0
2
2
0
0
1
2
0
0
5
0
0
1
2
1
0
1
0
1
1
1
0
0
1
2
0
0
0
1
1
0
0
0
1
3

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

25
0

0.3
0.0

(0.2, 0.4)
(0.0, 0.0)

23
1

0.3
0.0

(0.2, 0.4)
(0.0, 0.1)

CONFIDENTIAL
Page 236
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BNT162b2
2.7.4 Summary of Clinical Safety

Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Amyotrophic lateral sclerosis
Carpal tunnel syndrome
Cerebral infarction
Cerebrovascular accident
Cervicogenic headache
Dementia Alzheimer's typeDizziness
Guillain-Barre syndrome
Haemorrhagic stroke
Hemiplegic migraine
Idiopathic intracranial hypertension
Intraventricular haemorrhage
Ischaemic stroke
Optic neuritis
Paraesthesia
Peripheral nerve lesion
Spinal cord compression
Subarachnoid haemorrhage
Syncope
Toxic encephalopathy
Transient global amnesia
Transient ischaemic attack
Uraemic encephalopathync

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

0
1
0
4
0
0
1
0
0
0
2
0
2
2
1
1
0
4
2
1
1
2
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

1
0
1
1
1
1
1
1
1
1
0
1
2
0
1
0
1
1
4
0
0
3
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

PREGNANCY, PUERPERIUM AND PERINATAL
CONDITIONS
Abortion incomplete
Abortion spontaneous
Abortion spontaneous incomplete
Retained products of conception

2

0.0(0.0, 0.1)

6

0.1

(0.0, 0.2)

0
2
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
3
1
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

PSYCHIATRIC DISORDERS
Alcohol abuse
Bipolar disorder
Depression
Depression suicidal
Disorientation
Major depression
Mental disorder
Panic attack

5
0
0
1
0
1
0
1
0

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

9
1
2
1
1
0
1
0
1

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

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Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)

System Organ Class
Preferred Term

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Psychotic disorder
Suicidal ideation
Suicide attempt

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

1
0
1

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

0
2
1

0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

RENAL AND URINARY DISORDERS
Acute kidney injury
Hydronephrosis
Nephrolithiasis
Renal colic
Subcapsular renal haematoma
Ureterolithiasis
Urinary bladder polyp

11
2
0
6
1
1
1
0

0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

8
0
1
6
0
0
0
1

0.1
0.0
0.0
0.1
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

REPRODUCTIVE SYSTEM AND BREASTDISORDERS
Adnexal torsion
Breast hyperplasia
Endometriosis
Ovarian cyst
Ovarian mass
Rectocele
Uterine prolapse
Vaginal prolapse

20.0(0.0, 0.1)

5

0.1

(0.0, 0.1)

0
1
0
1
0
0
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

2
0
1
0
1
1
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

RESPIRATORY, THORACIC AND
MEDIASTINAL DISORDERS
Acute respiratory failure
AsthmaAsthmatic crisis
Chronic obstructive pulmonary disease
Dyspnoea
HypoxiaInterstitial lung disease
Nasal septum deviation
Pneumonia aspiration
Pneumonitis
Pneumothorax
Pulmonary embolism
Pulmonary mass
Respiratory arrest
Respiratory failure

14

0.2

(0.1, 0.3)

14

0.2

(0.1, 0.3)

2
1
0
3
0
0
1
1
1
1
0
5
0
0
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2
0
1
0
1
1
1
0
1
0
1
6
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

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Table 18. Incidence Rates of at Least 1 Serious Adverse Event From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Phase 2/3
Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)

System Organ Class
Preferred Term

BNT162b2 (30 μg)(Na=21926, TEb=83.4)
ncIR(95% CIe)d(/100 PY)

SOCIAL CIRCUMSTANCES
Miscarriage of partner

1
1

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

0
0

0.0
0.0

(0.0, 0.0)
(0.0, 0.0)

SURGICAL AND MEDICAL PROCEDURES
Finger amputation

1
1

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

0
0

0.0
0.0

(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS
Accelerated hypertension
Aortic aneurysm
Aortic rupture
Aortic stenosis
Arteriosclerosis
Deep vein thrombosis
Hypertension
Hypertensive crisis
Hypertensive emergency
Hypertensive urgency
Orthostatic hypotension
Peripheral artery stenosis

12
0
1
0
0
2
3
3
1
0
2
0
0

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.3)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

13
1
0
1
2
0
5
0
0
1
0
2
1

0.2
0.0
0.0
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

nc

Placebo(Na=21921, TEb=82.2)
IR(95% CIe)d(/100 PY)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:09)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 sae exp p3 saf

Subgroup Analyses
Overall, no clinically meaningful differences in IRs of SAEs were observed by baseline
SARS-CoV-2 status, ethnicity, race, or sex subgroups.
IRs of SAEs were similar by baseline SARS-CoV-2 status in the BNT162b2 and placebogroups for baseline positive (4.0 per 100 PY [95% CI: 1.9, 7.3] and 1.9 per 100 PY [95% CI:
0.6, 4.4]) and baseline negative (3.2 per 100 PY [95% CI: 2.8, 3.6] and 3.3 per 100 PY [95%
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CI: 2.9, 3.7]) participants. IRs of SAEs in the baseline positive BNT162b2 group weresimilar (4.0 per 100 PY [95% CI: 1.9, 7.3]) to those in the baseline negative BNT162b2
group (3.2 per 100 PY [95% CI: 2.8, 3.6]), and similar to what was observed in the overall
SAE analysis irrespective of baseline status (Table 7).
While there are differences in exposure (2.5 vs 80.4) by baseline SARS-CoV-2 positive andnegative status, respectively, IRs were numerically low or similar by baseline SARS-CoV-2
status, so there is no evidence that individuals who are positive at baseline report AEs at ahigher frequency than those who are negative at baseline.
IRs of SAEs were similar in the BNT162b2 and placebo groups for Hispanic/Latino (3.5 per
100 PY [95% CI: 2.8, 4.3] and 3.6 per 100 PY [95% CI: 2.9, 4.5]), Non-Hispanic/Non-Latino(3.1 per 100 PY [95% CI: 2.7, 3.6] for each), and Not Reported (2.4 per 100 PY [95% CI:
0.1, 13.1] and 2.3 per 100 PY [95% CI: 0.1, 12.7]) participants.

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IRs of SAEs were similar in the BNT162b2 and placebo groups for White (3.3 per 100 PY[95%CI: 2.9, 3.8]and 3.5 per 100 PY [95% CI: 3.1, 4.0]), Black or African American (2.5 per
100 PY [95% CI: 1.6, 3.9] and 2.6 per 100 PY [95% CI: 1.6, 4.0]), and greater in the
BNT162b2 group for All Others compared to placebo (2.7 per 100 PY [95% CI: 1.6, 4.3] and1.4 per 100 PY [95% CI: 0.6, 2.7]).
IRs of SAEs were similar by sex in the BNT162b2 and placebo groups for males (3.5 per
100 PY[95% CI: 3.0, 4.1] and 3.4 per 100 PY [95% CI: 2.8, 4.0]) and females (2.9 per
100 PY [95% CI: 2.4, 3.5] and 3.2 per 100 PY [95% CI: 2.6, 3.7]).
2.7.4.2.4.3.2.2.1. Participants with Confirmed Stable HIV Disease: Blinded
Placebo-Controlled Follow-Up Period From Dose 1 to the Unblinding Date (Phase 3,
Study C4591001, Serious Adverse Events)
From Dose 1 to the unblinding date, IRs of at least 1 SAE in participants with stable HIV
disease were similar in the BNT162b2 group (6.6 per 100 PY [95% CI:0.8, 23.9]) and theplacebo group (6.9 per 100 PY [95% CI: 0.8, 25.1]) with 2 participants reporting at least
1 SAE in each group. None of the SAEs were assessed by the investigator as related to study
intervention.
One older participant in the BNT162b2 group had an SAE of pneumonia 86 days
after Dose 2 which lasted 8 days and resolved.



One older participant in the BNT162b2 group had a fatal SAE of road traffic accident
73 days after Dose 2.



One younger participant in the placebo group had an SAE of breast cancer 71 days
after Dose 2 that was continuing at the data cutoff date.

One younger participant in the placebo group had an SAE of diabetes mellitus 68
days after Dose 2, and COVID-19 pneumonia 72 days after Dose 2 which lasted 4days and resulted in death (Section 2.7.4.2.4.3.1). The participant had a history ofasthma, HIV, hypertension, and obesity and then was diagnosed with diabetes
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mellitus 68 days after Dose 2. Four days after the diagnosis, the participant presented
in the ER with an elevated blood glucose level and was admitted. Laboratory tests on
the following day included a SARS-CoV-2 PCR test, which was positive. Two days
later, a second test confirmed the COVID-19 positive diagnosis. The following day,75 days after Dose 2, the participant died due to disease progression and COVID-19
pneumonia. The investigator concluded that the diabetes mellitus and COVID-19
pneumonia were not related to study intervention. This participant was diagnosed
based on a local COVID-19 test that could not be confirmed as protocol-approved
and was not confirmed by a test result from the central laboratory, therefore, thisparticipant was not included in efficacy analyses.
2.7.4.2.4.3.2.3. Open-Label Follow-Up Period – Original BNT162b2 Participants (Phase
3, Study C4591001, Serious Adverse Events)
From unblinding date to the data cutoff date, the IR of at least 1 SAE was 2.0 per 100 PY(95% CI: 1.5, 2.6) in original BNT162b2 participants (Table 19).

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One younger participant with no past medical history had a life-threatening SAE of
myocardial infarction 71 days after Dose 2 that was assessed by the investigator as related to
study intervention, which lasted 1 day and resolved the same day.

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Table 19. Incidence Rates of at Least 1 Serious Adverse Event From Unblinding Date
to Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population

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Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event55

2.0(1.5, 2.6)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Pancytopenia

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

CARDIAC DISORDERS
Atrial fibrillation
Atrial flutter
Cardiac failure congestive
Coronary artery occlusion
Myocardial infarction

8
1
1
1
1
4

0.3
0.0
0.0
0.0
0.0
0.1

(0.1, 0.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

EYE DISORDERS
Retinal tear

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

GASTROINTESTINAL DISORDERS
Abdominal pain upper
Haematemesis
Rectal haemorrhage

3
1
1
1

0.1
0.0
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Impaired healing

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

HEPATOBILIARY DISORDERS
Acute hepatic failure
Cholecystitis
Cholecystitis acute
Cholelithiasis obstructive
Portosplenomesenteric venous thrombosis

6
1
1
2
1
1

0.2
0.0
0.0
0.1
0.0
0.0

(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

INFECTIONS AND INFESTATIONSAppendicitis
Bacteraemia
Clostridium difficile colitis
Endocarditis
Herpes zoster oticus
Meningitis bacterial
Pneumonia
Post procedural infection
Postoperative abscess

10
1
1
1
1
1
1
1
1
1

0.4
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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Table 19. Incidence Rates of at Least 1 Serious Adverse Event From Unblinding Date
to Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

SepsisSubcutaneous abscess

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Ankle fracture
Burns second degree
Burns third degree
Clavicle fracture
Fall
Humerus fracture
InjuryProcedural dizziness
Procedural pain
Rib fracture
Road traffic accident

8
1
1
1
1
1
1
1
1
1
1
2

0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.1

(0.1, 0.6)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Osteoarthritis

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)
Adenocarcinoma pancreas
Brain cancer metastatic
Hormone receptor positive breast cancer
Metastases to lung
Pancreatic carcinoma metastatic
Uterine cancer

50.2(0.1, 0.4)

1
1
1
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NERVOUS SYSTEM DISORDERS
Dizziness
Intracranial aneurysm
Seizure

3
1
1
1

0.1
0.0
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS
Abortion spontaneous

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

PSYCHIATRIC DISORDERS
Bipolar I disorder

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

RENAL AND URINARY DISORDERS
Nephrolithiasis

2
2

0.1
0.1

(0.0, 0.3)
(0.0, 0.3)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

10.0(0.0, 0.2)

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Table 19. Incidence Rates of at Least 1 Serious Adverse Event From Unblinding Date
to Data Cutoff Date (13MAR2021), by System Organ Class and Preferred
Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived BNT162b2 – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population
Vaccine Group (as Administered)

System Organ Class
Preferred Termnc

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Endometrial thickening
Endometriosis

BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
AsthmaChronic obstructive pulmonary disease
Dyspnoea
Dyspnoea exertional
Pulmonary embolism

5
1
1
1
1
1

0.2
0.0
0.0
0.0
0.0
0.0

(0.1, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

VASCULAR DISORDERS
Aortic aneurysm
Arterial occlusive disease
Deep vein thrombosis

3
2
1
1

0.1
0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from the unblinding date to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 sae ex bnt p3 saf

2.7.4.2.4.3.2.4. Blinded Placebo-Controlled and Open-Label Follow-Up Periods to 6
Months After Dose 2 – Original BNT162b2 Participants (Phase 3, Study C4591001,
Serious Adverse Events)
From Dose 1 to 6 months after Dose 2, during the blinded and open-label follow-up periods,
190 (1.6%) participants in the BNT162b2 group reported at least 1 SAE (Table 20).

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Two of the SAEs in the BNT162b2 group (SIRVA and paraesthesia, see Section
2.7.4.2.4.3.2.1 and Section 2.7.4.2.4.3.2.2) were assessed by the investigator as related to
study intervention (Table 11)
The number of participants who reported at least 1 SAE was 73 (1.1%) and 117 (2.2%) in theyounger and older age groups, respectively.

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Comparison of SAEs reported from Dose 1 to 1 month after Dose 2 to SAEs reported from 1
month after Dose 2 to 6 months Dose 2 shows that the frequency of SAEs increased from
0.5% to 1.1%, respectively. The following SOCs had the largest increase in SAEs (Dose 1 to
1 month after Dose 2 vs 1 month after Dose 2 to 6 months after Dose 2):Neoplasms, benign, malignant, and unspecified (including cysts and polyps): 4(0.0%) vs 21 (0.2%)

Injury, poisoning, and procedural complications: 2 (0.0%) vs 14 (0.1%)

Infections and infestations: 14 (0.1%) vs 22 (0.2%)

Gastrointestinal disorders: 4 (0.0%) vs 10 (0.1%)

Respiratory, thoracic, and mediastinal disorders: 2 (0.0%) vs 8 (0.1%)

Hepatobiliary disorders: 3 (0.0%) vs 8 (0.1%)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Any event190 (1.6)(1.4, 1.8)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Pancytopenia

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Acute myocardial infarction
Atrial fibrillation
Myocardial infarction
Angina pectoris
Angina unstable
Cardiac failure congestive
Acute coronary syndrome
Arrhythmia supraventricularAtrial flutter
Bradycardia
Cardiac arrest
Coronary artery disease
Coronary artery occlusion
Pericarditis
Ventricular tachycardia

27 (0.2)
4 (0.0)4 (0.0)4 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
Vertigo1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

EYE DISORDERS
Choroidal neovascularisation
Diplopia
Ophthalmic vein thrombosis
Retinal tear

4 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GASTROINTESTINAL DISORDERS
ColitisGastritis
Small intestinal obstruction
Abdominal pain upper
Food poisoning
Gastrointestinal haemorrhage

14 (0.1)
2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Haematemesis
Haemorrhoids
Impaired gastric emptying
Intestinal obstruction
Obstructive pancreatitis
Pancreatitis

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONSChest pain
Non-cardiac chest pain
Asthenia
Shoulder injury related to vaccine administration
Vascular stent occlusion

7 (0.1)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

HEPATOBILIARY DISORDERS
Cholecystitis acute
Cholelithiasis
Bile duct stone
Biliary colic
Cholecystitis
Cholelithiasis obstructive
Portosplenomesenteric venous thrombosis

11 (0.1)
3 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Anaphylactic reaction
Drug hypersensitivity

2 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

INFECTIONS AND INFESTATIONSAppendicitis
Diverticulitis
Pneumonia
Cellulitis
Pyelonephritis
Abscess
Appendicitis perforated
Arthritis bacterial
Bacteraemia
Bacterial sepsis
Clostridium difficile colitis

36 (0.3)
10 (0.1)
3 (0.0)3 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.2, 0.4)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Device related infection
Empyema
Endocarditis
Escherichia urinary tract infection
Gangrene
Gastroenteritis
Herpes zoster oticus
Meningitis bacterial
Penile infection
Peritoneal abscess
Peritonitis
Peritonsillar abscess
Postoperative abscessSepsisSubcutaneous abscess
Urinary tract infection
INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Ankle fracture
Road traffic accident
Wrist fracture
Burns second degree
Burns third degree
Cervical vertebral fracture
Craniocerebral injury
Facial bones fracture
Fall
Head injury
Humerus fracture
Patella fracture
Pelvic fracture
Procedural dizzinessSpinal cord injury cervical
Tibia fracture
Traumatic intracranial haemorrhage
Upper limb fracture

1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

16 (0.1)
2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
INVESTIGATIONS
Cardiac stress test abnormal

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

METABOLISM AND NUTRITION DISORDERS
Diabetic ketoacidosis
Hypoglycaemia
Hypokalaemia

3 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Osteoarthritis
ArthritisIntervertebral disc compression
Intervertebral disc degeneration
Intervertebral disc protrusion
Osteochondritis

9 (0.1)4 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND
POLYPS)
Breast cancer
Invasive ductal breast carcinoma
Prostate cancer
Acute myeloid leukaemia
Adenocarcinoma pancreas
Adrenal gland cancer
Benign hydatidiform mole
Bladder cancer
Borderline serous tumour of ovary
Brain cancer metastatic
Breast cancer in situ
Carcinoid tumour of the stomach
Colon adenoma
Gallbladder cancer stage II
Gastric cancer
Malignant melanoma
Non-small cell lung cancer stage IV
Skin cancer
Squamous cell carcinoma
Thyroid cancer

25 (0.2)(0.1, 0.3)

2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Transitional cell carcinoma
Uterine cancer

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

NERVOUS SYSTEM DISORDERS
Subarachnoid haemorrhage
Cerebrovascular accident
Dizziness
Optic neuritis
Syncope
Transient ischaemic attack
Carpal tunnel syndrome
Idiopathic intracranial hypertension
Intracranial aneurysm
Ischaemic stroke
Paraesthesia
Peripheral nerve lesion
SeizureToxic encephalopathy
Transient global amnesia
Uraemic encephalopathy

23 (0.2)
3 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.1, 0.3)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS
Abortion spontaneous

2 (0.0)2 (0.0)(0.0, 0.1)
(0.0, 0.1)

PSYCHIATRIC DISORDERS
Suicide attempt

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

RENAL AND URINARY DISORDERS
Nephrolithiasis
Acute kidney injury
Renal colic
Subcapsular renal haematoma

9 (0.1)5 (0.0)2 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS
Breast hyperplasia
Endometrial thickening
Endometriosis
Ovarian cyst
Uterine prolapse

3 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

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Table 20. Number (%) of Subjects Reporting at Least 1 Serious Adverse Event From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (asAdministered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Pulmonary embolism
Chronic obstructive pulmonary disease
Dyspnoea
Dyspnoea exertional
Interstitial lung disease
Pneumonitis

10 (0.1)
4 (0.0)2 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SOCIAL CIRCUMSTANCES
Miscarriage of partner

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

SURGICAL AND MEDICAL PROCEDURES
Finger amputation

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS
Aortic aneurysm
Deep vein thrombosis
Arterial occlusive disease
Hypertension

6 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s130 pd2 ser p3 saf

2.7.4.2.4.3.2.5. Open-Label Follow-Up Period – Original Placebo Participants Who
Then Received BNT162b2 (Phase 3, Study C4591001, Serious Adverse Events)
From Dose 3 (first dose of BNT162b2) to the data cutoff date, the IR of at least 1 SAE inoriginal placebo participants who then received BNT162b2 was 2.7 per 100 PY (95% CI:
2.1, 3.5) (Table 21). One SAE was assessed by the investigator as related to study
intervention (Table 14).

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One participant in the younger age group with a history of food and seasonal allergies
and drug hypersensitivity), who was originally randomized to the placebo group andunblinded to receive BNT162b2, had an anaphylactoid reaction 2 days post Dose 3(first dose of BNT162b2), with an event duration of 1 day; the event was reported as
an SAE, reported as resolved, and the participant withdrew from the study.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

There were 2 participants who reported SAEs for baseline positive original placebo
participants who then received BNT162b2. A meaningful comparison with baseline negative
participants is not possible.

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Table 21. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event65

2.7(2.1, 3.5)

CARDIAC DISORDERS
Acute myocardial infarction
Arrhythmia
Arteriospasm coronary
Atrial fibrillation
Cardiac failure congestive
Cardio-respiratory arrest
Cardiovascular disorder
Ischaemic cardiomyopathy
Myocardial infarction

8
1
1
1
2
1
1
1
1
1

0.3
0.0
0.0
0.0
0.1
0.0
0.0
0.0
0.0
0.0

(0.1, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

CONGENITAL, FAMILIAL AND GENETIC DISORDERS
Hypertrophic cardiomyopathy

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

EAR AND LABYRINTH DISORDERS
Vertigo

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

EYE DISORDERS
Diplopia

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

GASTROINTESTINAL DISORDERS
Anal prolapse
Gastrointestinal haemorrhage
Gastrointestinal necrosis
Gastrooesophageal reflux disease
Intestinal obstruction
Intestinal ulcer perforation
Pancreatitis acute
Small intestinal obstruction

8
1
1
1
1
1
1
2
1

0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.1
0.0

(0.1, 0.7)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONSDrug withdrawal syndrome
Fatigue
Pelvic mass

3
1
1
1

0.1
0.0
0.0
0.0

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

HEPATOBILIARY DISORDERS
Cholecystitis
Hepatitis acute

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

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Table 21. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

IMMUNE SYSTEM DISORDERS
Anaphylactoid reaction

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

INFECTIONS AND INFESTATIONSAppendicitis perforated
COVID-19 pneumonia
Clostridium difficile infection
Focal peritonitis
Pelvic abscess
Pneumonia
Urosepsis

4
1
1
1
1
1
1
1

0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Ankle fracture
Fall
Lower limb fracture
Postoperative ileus
Scapula fracture
Spinal fracture
Traumatic intracranial haemorrhage

6
1
1
1
1
1
1
1

0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

METABOLISM AND NUTRITION DISORDERS
Diabetes mellitus inadequate control

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Myalgia
Osteoarthritis

4
1
3

0.2
0.0
0.1

(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.4)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)
Brain neoplasm
Breast cancer
Breast cancer stage II
Hepatic cancer
Non-small cell lung cancer stage III

50.2(0.1, 0.5)

1
1
1
1
1

0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NERVOUS SYSTEM DISORDERS
Brachial plexopathy
Cerebrovascular accident
SeizureSyncope

9
1
4
1
1

0.4
0.0
0.2
0.0
0.0

(0.2, 0.7)
(0.0, 0.2)
(0.0, 0.4)
(0.0, 0.2)
(0.0, 0.2)

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Table 21. Incidence Rates of at Least 1 Serious Adverse Event From Dose 3 to Data
Cutoff Date (13MAR2021), by System Organ Class and Preferred Term –Open-Label Follow-up Period – Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

Transient ischaemic attack

2

0.1(0.0, 0.3)

PSYCHIATRIC DISORDERS
Alcohol withdrawal syndrome
Anxiety
Bipolar disorder
Completed suicide
Depression
Major depression
Suicide attempt

5
1
1
1
1
1
1
1

0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

RENAL AND URINARY DISORDERS
Nephrolithiasis
Urinary tract obstruction

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Acute respiratory failure
Chronic obstructive pulmonary disease
Dyspnoea
Pulmonary embolism

8
2
1
1
4

0.3
0.1
0.0
0.0
0.2

(0.1, 0.7)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.4)

VASCULAR DISORDERS
Aortic stenosis
Deep vein thrombosis
Hypertension
Thrombosis

5
1
2
1
1

0.2
0.0
0.1
0.0
0.0

(0.1, 0.5)
(0.0, 0.2)
(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

Note: Dose 3 = First dose of BNT162b2 (30 μg).
Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 3 to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 sae exp p3x saf

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2.7.4.2.4.3.2.5.1. Original Placebo Participants, had COVID-19 Occurrence After Dose
1, and Then Received BNT162b2 (Phase 3, Study C4591001, Serious Adverse Events)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)For original placebo participants who had COVID-19 occurrence after Dose 1 and thenreceived BNT162b2, the IR for at least 1 SAE was 3.4 per 100 PY (95% CI: 0.7, 10.0). These
SAEs occurred in 3 participants.
One participant with a significant past history of a deep vein thrombosis and COVID19 in the placebo-controlled follow-up period, had a Grade 3 SAE of pulmonary
embolism, 6 days post Dose 4, which lasted 2 days and resolved with sequelae. The
SAE was assessed as not related to the study intervention by the investigator.



One participant with a past medical history of hypertension, hypercholesterolemia,
coronary artery disease, and a coronary artery bypass in 2006, had a Grade 3 SAE of
myocardial infarction, 16 days post Dose 3, which lasted 4 days and resolved withsequelae. The SAE was assessed and not related to the study intervention by theinvestigator.



One participant in the older age group had 4 SAEs:
o 2 Grade 3 SAEs, urosepsis and acute hypoxic respiratory failure, both
occurred 7 days post Dose 3, lasted 5 days, and resolved. These SAEs wereassessed as not related to the study intervention by the investigator.
o Grade 3 SAE of non-small cell lung cancer (stage III), occurred 31 days post
Dose 4 and was continuing at the data cutoff date. This SAE was assessed as
not related to the study intervention by the investigator.
o Grade 2 SAE of Clostridium difficile infection occurred 47 days post Dose 4
and was continuing at the data cutoff date. This SAE was assessed as not
related to the study intervention by the investigator.

2.7.4.2.4.3.2.6. Serious Adverse Event Narratives (Phase 3, Study C4591001)
Narratives for the Phase 3 participants who reported SAEs assessed as related to study
intervention by the investigator who completed their visit at 1 month after Dose 2 andthrough the data cutoff date (13 March 2021) are provided (see Section 2.7.4.2.4.4).
2.7.4.2.4.3.3. Safety-Related Participant Withdrawals (Phase 3, Study C4591001)
Details and outputs regarding safety-related participant withdrawals for Phase 3 ofStudy C4591001 are in Module 5.3.5.1 C4591001 6-Month Update CSR Section 12.2.4.3.
In this ongoing study, tables summarizing participant withdrawals may include someparticipants who were reported as withdrawn but remain in the study and are continuing to beevaluated. These participants are documented in Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Errata.

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2.7.4.2.4.3.3.1. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to 1 Month
After Dose 2 (Phase 3, Study C4591001, Safety-Related Participant Withdrawals)
From Dose 1 to 1 month after Dose 2, few participants in the BNT162b2 group (0.1%) and in
the placebo group (0.2%) were withdrawn because of AEs (Table 22).

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

There were 32 participants in the BNT162b2 group and 36 participants in the placebo group
had an AE leading to withdrawal, which included:

6 participants in the BNT162b2 group and 2 participants in the placebo group who
withdrew from the study due to AEs in the SOC of General Disorders andAdministration Site Conditions (BNT162b2 group: injection site pain [2 participants]
and chills, facial pain, injection site dermatitis, injection site swelling, pyrexia, andswelling face [1 participant each]; placebo group: death and fatigue [1 participanteach]).



5 participants in the BNT162b2 group and 6 participants in the placebo groupwithdrew from the study due to AEs in the SOC of Injury, Poisoning and Procedural
Complications (BNT162b2 group: exposure during pregnancy, maternal exposure
during pregnancy [2 participants each] and alcohol poisoning [1 participant]; placebogroup: exposure during pregnancy [5 participants] and overdose [1 participant].



3 participants in the BNT162b2 group and 5 participants in the placebo groupwithdrew from the study due to AEs in the SOC Cardiac Disorders (BNT162b2
group: cardiac arrest, coronary artery disease and tachycardia [1 participant each];placebo group: atrial fibrillation [2 participants], cardiac failure congestive, coronary
artery occlusion, and myocardial infarction [1 participant each]).



3 participants in the BNT162b2 group and 6 participants in the placebo groupwithdrew from the study due to AEs in the SOC of Nervous System Disorders(BNT162b2 group: headache [3 participants]; placebo group: dizziness [2participants], amnesia, cerebral infarction, hemorrhagic stroke, paraparesis, andParkinsonism [1 participant each]).



3 participants in the BNT162b2 group and 6 participants in the placebo groupwithdrew from the study due to AEs in the SOC of Gastrointestinal Disorders(BNT162b2 group: abdominal pain upper, gastrointestinal haemorrhage, andparaesthesia oral [1 participant each]; placebo group: diarrhoea [2 participants],
diverticular perforation, dry mouth, dysphagia, and nausea [1 participant each]).



3 participants in the BNT162b2 group and 1 participant in the placebo groupwithdrew from the study due to AEs in the SOC of Neoplasms Benign, Malignant andUnspecified (incl Cysts and Polyps) (BNT162b2 group:adenocarcinoma gastric,
lymphoproliferative disorder, and metastases to central nervous system [1 participanteach]; placebo group: biliary cancer metastatic and metastases to liver [1 participanteach]).

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BNT162b2
2.7.4 Summary of Clinical Safety

1 participant each in the BNT162b2 group and the placebo group withdrew from thestudy due to AEs in the SOC of Ear and Labyrinth Disorders (BNT162b2 group:
deafness unilateral [1 participant]; placebo group: vertigo [1 participant]).



1 participant each in the BNT162b2 group and the placebo group withdrew from thestudy due to AEs in the SOC of Musculoskeletal and Connective Tissue Disorders(myalgia [1 participant in each group]).

No participant in the BNT162b2 group and 2 participants in the placebo groupwithdrew from the study due to AEs in the SOC of Immune System Disorders(placebo group: drug hypersensitivity [2 participants]).



1 participant in the BNT162b2 group and no participants in the placebo groupwithdrew from the study due to an AE in the SOC of Blood and Lymphatic System
Disorders (BNT162b2 group: lymphadenopathy [1 participant]).



1 participant each in the BNT162b2 group and the placebo group withdrew from thestudy due to AEs in the SOC of Eye Disorders (BNT162b2 group: eye pain [1participant]; placebo group: visual impairment [1 participant]).



1 participant in the BNT162b2 group and no participants in the placebo groupwithdrew from the study due to an AE in the SOC of Infections and Infestations(BNT162b2 group: Shigella sepsis [1 participant]).



No participants in the BNT162b2 group and 1 participant in the placebo groupwithdrew from the study due to an AE in the SOC of Investigations (placebo group:
irregular heart rate [1 participant]).

No clinically meaningful differences in AEs leading to withdrawal were observed by age
subgroups.

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Table 22. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

Placebo(Na=21921)
nb (%)(95% CIc)

Any event

32 (0.1)(0.1, 0.2)

36 (0.2)(0.1, 0.2)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymphadenopathy

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Atrial fibrillation
Cardiac arrest
Cardiac failure congestive
Coronary artery disease
Coronary artery occlusion
Myocardial infarction
Tachycardia

3 (0.0)01 (0.0)01 (0.0)001 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

5 (0.0)2 (0.0)01 (0.0)01 (0.0)1 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
Deafness unilateral
Vertigo1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

EYE DISORDERS
Eye pain
Visual impairment

1 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GASTROINTESTINAL DISORDERS
Diarrhoea
Abdominal pain upper
Diverticular perforation
Dry mouth
Dysphagia
Gastrointestinal haemorrhage
NauseaParaesthesia oral

3 (0.0)01 (0.0)000
1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

6 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)01 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

GENERAL DISORDERS AND ADMINISTRATION SITE
CONDITIONSInjection site pain
ChillsDeath
Facial pain
Fatigue
Injection site dermatitis

6 (0.0)(0.0, 0.1)

2 (0.0)(0.0, 0.0)

2 (0.0)1 (0.0)01 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)00
1 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

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Table 22. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Injection site swelling
Pyrexia
Swelling face

Placebo(Na=21921)
nb (%)(95% CIc)

1 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)000(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Drug hypersensitivity

00(0.0, 0.0)
(0.0, 0.0)

2 (0.0)2 (0.0)(0.0, 0.0)
(0.0, 0.0)

INFECTIONS AND INFESTATIONS
Shigella sepsis

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

INJURY, POISONING AND PROCEDURAL COMPLICATIONSExposure during pregnancy
Maternal exposure during pregnancy
Alcohol poisoning
Overdose

5 (0.0)2 (0.0)2 (0.0)1 (0.0)0(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

6 (0.0)5 (0.0)001 (0.0)(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)00(0.0, 0.0)
(0.0, 0.0)

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

MUSCULOSKELETAL AND CONNECTIVE TISSUEDISORDERS
Myalgia

1 (0.0)(0.0, 0.0)

1 (0.0)(0.0, 0.0)

1 (0.0)(0.0, 0.0)

1 (0.0)(0.0, 0.0)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED(INCL CYSTS AND POLYPS)
Adenocarcinoma gastricBiliary cancer metastatic
Lymphoproliferative disorder
Metastases to central nervous system
Metastases to liver

3 (0.0)(0.0, 0.0)

1 (0.0)(0.0, 0.0)

1 (0.0)01 (0.0)1 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)01 (0.0)001 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

NERVOUS SYSTEM DISORDERS
HeadacheDizziness
Amnesia
Cerebral infarction
Haemorrhagic stroke
Paraparesis
Parkinsonism

3 (0.0)3 (0.0)
0
0
0
0
0
0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

6 (0.0)02 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)1 (0.0)(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

PSYCHIATRIC DISORDERS
Depression
Depression suicidal
Panic attack

2 (0.0)1 (0.0)01 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)01 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

INVESTIGATIONSHeart rate irregular

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Table 22. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred
Term – Blinded Placebo-Controlled Follow-up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926)bn (%)(95% CIc)

System Organ Class
Preferred Term
Suicide attempt0(0.0, 0.0)

1 (0.0)(0.0, 0.0)000(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Urticaria
Diabetic footEczemaPruritus
Rash maculo-papular

2 (0.0)1 (0.0)1 (0.0)00
0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

3 (0.0)2 (0.0)01 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

VASCULAR DISORDERS
Hypertension
Arteriosclerosis

2 (0.0)1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

2 (0.0)2 (0.0)0(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Pulmonary embolism
Respiratory arrest

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Placebo(Na=21921)
nb (%)(95% CIc)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:10)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s130_1md2_wd_p3_saf

2.7.4.2.4.3.3.2. Blinded Placebo-Controlled Follow-Up Period From Dose 1 to the
Unblinding Date (Phase 3, Study C4591001, Safety-Related Participant Withdrawals)
From Dose 1 to the unblinding date, the IRs of participants withdrawn because of AEs were
0.5 per 100 PY in the BNT162b2 group and 0.6 per 100 PY in the placebo group (Table 23).
There were 45 participants in the BNT162b2 group and 51 participants in the placebo group
had an AE leading to withdrawal, which included:

9 participants in the BNT162b2 group and 8 participants in the placebo groupwithdrew from the study due to AEs in the SOC Cardiac Disorders (BNT162b2
group: cardiac arrest [4 participants]; cardiac failure congestive, cardio-respiratoryarrest, coronary artery disease, hypertensive heart disease and tachycardia [1participant each]; placebo group: atrial fibrillation and myocardial infarction [2
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participants each]; cardiac arrest, cardiac failure congestive, cardio respiratory arrest,and coronary artery occlusion [1 participant each]).


3 participants in the BNT162b2 group and 6 participants in the placebo groupwithdrew from the study due to AEs in the SOC of Gastrointestinal Disorders(BNT162b2 group: abdominal pain upper, gastrointestinal haemorrhage, andparaesthesia oral [1 participant each]; placebo group: diarrhoea [2 participants],
diverticular perforation, dry mouth, dysphagia, and nausea [1 participant each]).



7 participants in the BNT162b2 group and 2 participants in the placebo groupwithdrew from the study due to AEs in the SOC of General Disorders andAdministration Site Conditions (BNT162b2 group: injection site pain [2 participants],
chills, facial pain, injection site dermatitis, injection site swelling, pyrexia, sudden
cardiac death and swelling face [1 participant each]; placebo group: death and fatigue[1 participant each]).



4 participants in the BNT162b2 group and 3 participants in the placebo groupwithdrew from study due to AEs in the SOC Infections and Infestations (BNT162b2
group: COVID-19 pneumonia, emphysematous cholecystitis, sepsis, septic shock andShigella sepsis [1 participant each]; placebo group: COVID-19, pneumonia, andseptic shock [1 participant each]).

No clinically meaningful differences in IRs of AEs leading to withdrawal were observed in
the younger and older age groups.

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2.7.4 Summary of Clinical Safety

Table 23. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)

System Organ Class
Preferred Term

BNT162b2 (30 μg)
Placebo(Na=21926, TEb=83.4)(Na=21921, TEb=82.2)
ncIR(95% CIe) nc
IR(95% CIe)dd(/100 PY)(/100 PY)

Any event45

0.5(0.4, 0.7)

51

0.6

(0.5, 0.8)

BLOOD AND LYMPHATIC SYSTEM DISORDERS
Lymphadenopathy

1
1

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

0
0

0.0
0.0

(0.0, 0.0)
(0.0, 0.0)

CARDIAC DISORDERS
Atrial fibrillation
Cardiac arrest
Cardiac failure congestive
Cardio-respiratory arrest
Coronary artery disease
Coronary artery occlusion
Hypertensive heart disease
Myocardial infarction
Tachycardia

9
0
4
1
1
1
0
1
0
1

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

8
2
1
1
1
0
1
0
2
0

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

EAR AND LABYRINTH DISORDERS
Deafness unilateral
Vertigo

1
1
0

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

1
0
1

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

EYE DISORDERS
Eye pain
Visual impairment

1
1
0

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

1
0
1

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

GASTROINTESTINAL DISORDERS
Abdominal pain upper
Diarrhoea
Diverticular perforation
Dry mouth
Dysphagia
Gastrointestinal haemorrhage
NauseaParaesthesia oral

3
1
0
0
0
0
1
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

6
0
2
1
1
1
0
1
0

0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

GENERAL DISORDERS AND ADMINISTRATION
SITE CONDITIONSChillsDeath
Facial pain
Fatigue
Injection site dermatitis
Injection site pain

7

0.1

(0.0, 0.2)2

0.0

(0.0, 0.1)

1
0
1
0
1
2

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

0
1
0
1
0
0

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

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BNT162b2
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Table 23. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
Placebo(Na=21926, TEb=83.4)(Na=21921, TEb=82.2)
ncIR(95% CIe) nc
IR(95% CIe)dd(/100 PY)(/100 PY)

System Organ Class
Preferred Term

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Injection site swelling
Pyrexia
Sudden cardiac death
Swelling face

1
1
1
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

0
0
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)

IMMUNE SYSTEM DISORDERS
Drug hypersensitivity

0
0

0.0
0.0

(0.0, 0.0)
(0.0, 0.0)

2
2

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

INFECTIONS AND INFESTATIONSCOVID-19
COVID-19 pneumonia
Emphysematous cholecystitis
Pneumonia
Sepsis
Septic shock
Shigella sepsis

4
0
1
1
0
1
1
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

3
1
0
0
1
0
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

INJURY, POISONING AND PROCEDURALCOMPLICATIONS
Alcohol poisoning
Exposure during pregnancy
Maternal exposure during pregnancy
Overdose

50.1(0.0, 0.1)

10

0.1

(0.1, 0.2)

1
2
2
0

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)

0
8
1
1

0.0
0.1
0.0
0.0

(0.0, 0.0)
(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)

INVESTIGATIONSHeart rate irregular

0
0

0.0
0.0

(0.0, 0.0)
(0.0, 0.0)

1
1

0.0
0.0

(0.0, 0.1)
(0.0, 0.1)

MUSCULOSKELETAL AND CONNECTIVE TISSUEDISORDERS
Myalgia10.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

1

0.0

(0.0, 0.1)

1

0.0

(0.0, 0.1)

NEOPLASMS BENIGN, MALIGNANT AND
UNSPECIFIED (INCL CYSTS AND POLYPS)
Adenocarcinoma gastricBiliary cancer metastatic
Breast cancer
Lung cancer metastatic
Lymphoproliferative disorder
Malignant melanoma
Metastases to central nervous system
Metastases to liver

40.0(0.0, 0.1)

3

0.0

(0.0, 0.1)

1
0
0
1
1
0
1
0

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

0
1
1
0
0
1
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

NERVOUS SYSTEM DISORDERS
Amnesia
Cerebral infarction

3
0
0

0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

7
1
1

0.1
0.0
0.0

(0.0, 0.2)
(0.0, 0.1)
(0.0, 0.1)

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BNT162b2
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Table 23. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
Placebo(Na=21926, TEb=83.4)(Na=21921, TEb=82.2)
ncIR(95% CIe) nc
IR(95% CIe)dd(/100 PY)(/100 PY)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Dementia Alzheimer's typeDizziness
Haemorrhagic stroke
HeadacheParaparesis
Parkinsonism

0
0
0
3
0
0

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
2
1
0
1
1

0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

PSYCHIATRIC DISORDERS
Depression
Depression suicidal
Panic attack
Suicide attempt

2
1
0
1
0

0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)

2
0
1
0
1

0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

RESPIRATORY, THORACIC AND MEDIASTINALDISORDERS
Acute respiratory failure
Chronic obstructive pulmonary disease
Pulmonary embolism
Respiratory arrest

1

0.0(0.0, 0.1)

3

0.0

(0.0, 0.1)

0
1
0
0

0.0
0.0
0.0
0.0

(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)

1
0
1
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dermatitis
Diabetic footEczemaPruritus
Rash maculo-papular
Urticaria

3
1
1
0
0
0
1

0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)

3
0
0
1
1
1
2

0.0
0.0
0.0
0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.1)

VASCULAR DISORDERS
Aortic rupture
Arteriosclerosis
Hypertension

3
0
2
1

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)
(0.0, 0.1)

3
1
0
2

0.0
0.0
0.0
0.0

(0.0, 0.1)
(0.0, 0.1)
(0.0, 0.0)
(0.0, 0.1)

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BNT162b2
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Table 23. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 1 to Unblinding Date, by System Organ Class and Preferred Term –Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term

BNT162b2 (30 μg)
Placebo(Na=21926, TEb=83.4)(Na=21921, TEb=82.2)
ncIR(95% CIe) nc
IR(95% CIe)dd(/100 PY)(/100 PY)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:09)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adae s131 wd exp p3 saf

2.7.4.2.4.3.3.3. Open-Label Follow-Up Period – Original BNT162b2 Participants (Phase
3, Study C4591001, Safety-Related Participant Withdrawals)
From the unblinding date to the data cutoff date, IRs of original BNT162b2 participants
withdrawn because of AEs were 0.1 per 100 PY (Table 24).

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BNT162b2
2.7.4 Summary of Clinical Safety

Table 24. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Unblinding Date to Data Cutoff Date (13MAR2021), by System OrganClass and Preferred Term – Open-Label Follow-up Period – Subjects
Who Originally Received BNT162b2 – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=20309, TEb=27.7)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event

40.1(0.0, 0.4)

CARDIAC DISORDERS
Myocardial infarction

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

HEPATOBILIARY DISORDERS
Acute hepatic failure

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS
InjuryRoad traffic accident

1
1
1

0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)
Metastases to lung1

0.0

(0.0, 0.2)

1

0.0

(0.0, 0.2)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from the unblinding date to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s131_wd_exp_bnt_p3_saf

2.7.4.2.4.3.3.4. Blinded Placebo-Controlled and Open-Label Follow-Up Periods to 6
Months After Dose 2 – Original BNT162b2 Participants (Phase 3, Study C4591001,
Safety-Related Participant Withdrawals)
From Dose 1 to 6 months after Dose 2 during the blinded and open-label follow-up period,
1 participant in the older BNT162b2 group was reported as withdrawn because of AEs(dermatitis) (Table 25). However, this participant remains in the study as the withdrawal was
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subsequently queried and corrected, as described in Module 5.3.5.1 C4591001 6-Month
Update Interim CSR Errata.

Table 25. Number (%) of Subjects Withdrawn Because of Adverse Events From
Dose 1 to 6 Months After Dose 2, by System Organ Class and Preferred
Term – Subjects With at Least 6 Months of Follow-up Time After Dose 2– Phase 2/3 Subjects ≥16 Years of Age (Subjects Who OriginallyReceived BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)bn (%)(95% CIc)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Term
Any event

1 (0.0)(0.0, 0.0)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dermatitis

1 (0.0)1 (0.0)(0.0, 0.0)
(0.0, 0.0)

Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
c. Exact 2-sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 27MAR2021(02:16)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adae_s130_pd2_wd_p3_saf

2.7.4.2.4.3.3.5. Open-Label Follow-Up Period – Original Placebo Participants Who
Then Received BNT162b2 (Phase 3, Study C4591001, Safety-Related Participant
Withdrawals)
From Dose 3 data to the data cutoff date, IR of original placebo participants withdrawn
because of AEs was 0.8 per 100 PY (Table 26).

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Table 26. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 3 to Data Cutoff Date (13MAR2021), by System Organ Class andPreferred Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived Placebo and Then Received BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years of Age – Safety Population

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

System Organ Class
Preferred Termnc

Any event190.8(0.5, 1.2)

CARDIAC DISORDERS
Angina pectoris
Cardio-respiratory arrest

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

GASTROINTESTINAL DISORDERS
Diarrhoea
Gastrointestinal haemorrhage

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONSChillsFatigue
Injection site pain
Pain

7
2
2
3
1

0.3
0.1
0.1
0.1
0.0

(0.1, 0.6)
(0.0, 0.3)
(0.0, 0.3)
(0.0, 0.4)
(0.0, 0.2)

IMMUNE SYSTEM DISORDERS
Allergy to vaccine
Anaphylactoid reaction

2
1
1

0.1
0.0
0.0

(0.0, 0.3)
(0.0, 0.2)
(0.0, 0.2)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS
Maternal exposure during pregnancy

3
3

0.1
0.1

(0.0, 0.4)
(0.0, 0.4)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Myalgia

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS
AND POLYPS)
Hepatic cancer

10.0(0.0, 0.2)

1

0.0

(0.0, 0.2)

NERVOUS SYSTEM DISORDERS
Headache

2
2

0.1
0.1

(0.0, 0.3)
(0.0, 0.3)

PSYCHIATRIC DISORDERS
Completed suicide

1
1

0.0
0.0

(0.0, 0.2)
(0.0, 0.2)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Angioedema
Urticaria

1
1
1

0.0
0.0
0.0

(0.0, 0.2)
(0.0, 0.2)
(0.0, 0.2)

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Table 26. Incidence Rates of Subjects Withdrawn Because of Adverse Events From
Dose 3 to Data Cutoff Date (13MAR2021), by System Organ Class andPreferred Term – Open-Label Follow-up Period – Subjects Who OriginallyReceived Placebo and Then Received BNT162b2 After Unblinding –Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

System Organ Class
Preferred Termnc

BNT162b2 (30 μg)(Na=19525, TEb=23.8)
IR (/100 PY)d(95% CIe)

Note: Dose 3 = First dose of BNT162b2 (30 μg).
Note: MedDRA (v23.1) coding dictionary applied.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 3 to data cutoff date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event. For "any event," n = number of subjects
reporting at least 1 occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 31MAR2021(18:33)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA1/adae s131 wd exp p3x saf

2.7.4.2.4.3.3.6. Narratives of Safety-Related Participant Withdrawals (Phase 3, Study
C4591001)
Narratives for the Phase 2/3 participants with any AEs leading to withdrawal from the study
through the data cutoff date (13 March 2021) are provided (see Section 2.7.4.2.4.4).
2.7.4.2.4.3.4. Other Significant Adverse Events (Phase 3, Study C4591001)
AEs of clinical interest were evaluated based on regulatory agency feedback and sponsor
medical review. Terms requested for analysis by the FDA were summarize and detailed forany such cases reported. Other terms of clinical interest, such as the CDC's list of AESIs for
COVID-19 vaccines, which both include terms potentially indicative of severe COVID-19 orserious autoimmune and neuroinflammatory disorders, were considered in the review ofreported events. Numerical imbalances for AESIs were based on the evaluation of AEs in theblinded placebo-controlled period. These safety evaluations are summarized below.
2.7.4.2.4.3.4.1. FDA-Requested Adverse Events of Clinical Interest
Safety evaluations were conducted for AEs of clinical interest: anaphylaxis, Bell’s Palsy,
lymphadenopathy, and appendicitis based on feedback from the FDA. These are summarized
by term below.

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2.7.4.2.4.3.4.1.1. Hypersensitivity/Anaphylaxis
During the blinded placebo-controlled follow-up period of Study C4591001 in participants≥16 years of age, there were 3 allergic reactions reported as SAEs (previously reported at
14 November cutoff date):Anaphylactic reaction following a bee sting in a BNT162b2 recipient (8 days after
Dose 2)

Drug hypersensitivity to an antibiotic in a BNT162b2 recipient (9 days after Dose 2)

Anaphylactic shock due to an ant bite in a placebo recipient (18 days after Dose 2).

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All 3 cases of allergic reaction above were considered by the investigator as not related to
study treatment.
During the open-label observational follow-up period of this study in participants ≥16 yearsof age, 1 participant who received BNT162b2 at Dose 3 (after originally being randomized toplacebo) experienced an SAE of anaphylactoid reaction, which was assessed as related to
study intervention. This participant (Subject C4591001 1129 11291260) was a female
adolescent with a medical history significant for multiple allergies since infancy. Two days
after Dose 3, the participant experienced hives on the left arm (deltoid) and self-administeredan epinephrine pen 24 minutes later (given the history of anaphylaxis to multiple allergens).
Six minutes after injection, the participant experienced shortness of breath. Hives andshortness of breath resolved within 10 and 30 minutes, respectively, of epinephrine
treatment. The participant did not seek additional medical attention. As a result of theanaphylactoid reaction, the participant was permanently withdrawn from the study.
Narratives for the events of anaphylactic reaction and anaphylactic shock are provided in
Module 5.3.5.1 C4591001 6-Month Update Interim CSR Section 14 Anaphylaxis (seeSubject C4591001 1261 12611006 for the participant with the SAE of drug hypersensitivity).
Hypersensitivity is also assessed as a CDC-defined AESI in Section 2.7.4.2.4.3.4.2.
2.7.4.2.4.3.4.1.2. Bell’s Palsy/Facial Paralysis
During the blinded placebo-controlled follow-up period in participants ≥16 years of age,
there were 6 adults who developed one-sided facial paralysis (Bell’s palsy, including facialparesis): 4 were randomized to BNT162b2 (all male) and 2 were randomized to placebo(1 male; 1 female). Regarding the 4 vaccinated participants (previously reported at
14 November 2020 cutoff date), their ages ranged from 40 to 70 (71 to 73 years of age inplacebo participants). Events began from 3 to 48 days after their last dose, were mild tomoderate in severity (moderate in the placebo participants), and duration ranged from 3 to 68
days (15 days in 1 placebo participant and ongoing in the other). Of the 4 cases inparticipants randomized to BNT162b2, 2 were considered by the investigator to be related to
study intervention. The remaining 4 cases (2 in participants originally randomized to
BNT162b2 and 2 in participants originally randomized to placebo) were assessed as not
related to study intervention.
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During the open-label observational follow-up period in participants ≥16 years of age,
3 participants who received BNT162b2 at Dose 3 or Dose 4 (were originally randomized toplacebo) experienced facial paralysis (Subjects 12471244, 10071441, and 12181015). All
were female and their ages ranged from 19 to 34 years. Events began 3 to 8 days after Dose 3
and were mild to severe in severity. One case had a duration of 12 days while the other2 were ongoing as of the data cutoff date. All these events of facial paralysis were consideredby the investigator as related to study intervention.
During the open-label follow-up period for participants originally randomized to BNT162b2,
a 51 year old male developed Bell’s palsy 154 days after receiving Dose 2.
Narratives for these events are provided in Module 5.3.5.1 C4591001 6-Month Update
Interim CSR Section 14 Bell’s Palsy.
Bell’s palsy is also assessed as an AESI in Section 2.7.4.2.4.3.4.3.

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2.7.4.2.4.3.4.1.3. Lymphadenopathy
During the blinded placebo-controlled follow-up period in participants ≥16 years of age,
lymphadenopathy was reported in 87 (1.0 per 100 PY) participants in the BNT162b2 groupcompared to 8 (0.1 per 100 PY) participants in the placebo group. The majority of eventswere mild to moderate; only 3 severe events of lymphadenopathy were reported (all in the
BNT162b2 group). The median onset of lymphadenopathy after Dose 1 and before Dose 2
was 5.5 days in the BNT162b2 group and 5.0 days in the placebo group; median onset after
Dose 2 was shorter in the BNT162b2 group versus the placebo group (2.0 days vs 7.0 days).
The median duration of lymphadenopathy was 5.5 days in the BNT162b2 group and 4.0 daysin the placebo group. As previously reported in the final analysis interim C4591001 CSR
dated 03 December 2020, 1 was a related SAE.
Narratives for these events (including those reported during the open-label follow-up period)
are located in Module 5.3.5.1 C4591001 6-Month Update Interim CSR Section 14
Lymphadenopathy (see Subject C4591001 1178 11781107 for the narrative of the participant
with the related SAE).
2.7.4.2.4.3.4.1.4. Appendicitis
Cases of appendicitis were examined in the placebo-controlled period of the study (including
PTs of appendicitis perforated and complicated appendicitis). There were 14 cases ofappendicitis and 1 case of appendicitis perforated in the BNT162b2 group, and 9 cases ofappendicitis, 2 cases of complicated appendicitis, and 1 appendicitis perforated in the placebogroup. Appendicitis cases were all reported as SAEs, and none of the cases were consideredrelated to study intervention.
Narratives for these events are in Module 5.3.5.1 C4591001 6-Month Update Interim CSR
Section 14 Appendicitis.

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2.7.4.2.4.3.4.2. CDC Adverse Events of Special Interest – Select Standard MedDRA
Queries for COVID-19
CDC-defined AESIs associated with COVID-19 vaccination were evaluated in the blinded
placebo-controlled period of the study, where reported in the Phase 2/3 safety population.
After a review of AEs using the CDC’s AESI list, the following terms were not foundreported in the study: acute disseminated encephalomyelitis, transverse myelitis, multiple
sclerosis, chronic inflammatory demyelinating polyneuropathy, encephalitis, myelitis,
encephalomyelitis, meningoencephalitis, ataxia, narcolepsy, cataplexy, immune
thrombocytopenia, thrombotic thrombocytopenic purpura, disseminated intravascular
coagulation, Kawasaki disease, multisystem inflammatory syndrome in children (MIS-C) andin adults (MIS-A), and acute respiratory distress syndrome.

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There were 2 cases of bacterial meningitis reported but they were not analyzed further as
there is an immediate and self-evident cause to their illness.
Terms that were present in the safety population are summarized below. For a given SMQ, if
there was no imbalance between the BNT162b2 group versus placebo, the PTs within the
SMQ were not further examined. In the case of an imbalance, the PTs responsible for theimbalance are further described and the nature of the events characterized with regard toplausible associated with vaccination.
Overall, the number and percentage of participants with any unsolicited AEs within theselected SMQs was similar in the BNT162b2 (224 [1.02%]) and placebo (217 [0.99%])
groups from Dose 1 to the unblinding date (Table 27).
From analysis of terms corresponding to AESIs from the CDC’s list, individual SMQs are
discussed below.

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Table 27. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30μg)(Na=21926)

Placebo(Na=21921)

nb (%)

nb (%)

Subjects with any unsolicited adverse events within
SMQ

224 (1.02)

217 (0.99)

Any unsolicited adverse events within Angioedema(SMQ)

30 (0.14)

29 (0.13)

2 (0.01)2 (0.01)0

1 (0.00)

Eye swelling0

1 (0.00)

Eyelid oedema

1 (0.00)

0

SMQ

Angioedema (SMQ)

Overall SMQ
System Organ Class
Preferred Term

Eye disorders

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Conjunctival oedema

Swelling of eyelid

1 (0.00)

0

Gastrointestinal disorders

6 (0.03)3 (0.01)

Gingival swelling0

1 (0.00)

Lip oedema

1 (0.00)

0

Lip swelling

2 (0.01)1 (0.00)

Swollen tongue

2 (0.01)1 (0.00)

Tongue oedema

1 (0.00)

0

General disorders and administration site conditions

4 (0.02)

7 (0.03)

Face oedema

2 (0.01)0

Swelling face

2 (0.01)7 (0.03)1 (0.00)

3 (0.01)

Respiratory, thoracic and mediastinal disorders
Pharyngeal swelling
Skin and subcutaneous tissue disorders

3 (0.01)18 (0.08)

Angioedema

3 (0.01)2 (0.01)

Urticaria

18 (0.08)

15 (0.07)

Urticaria papular
Arthritis (SMQ)

1 (0.00)
21 (0.10)

Any unsolicited adverse events within Arthritis (SMQ)
Infections and infestations
Arthritis bacterial
Metabolism and nutrition disorders
Gout
Musculoskeletal and connective tissue disorders01 (0.00)35 (0.16)

48 (0.22)

1 (0.00)01 (0.00)05 (0.02)3 (0.01)5 (0.02)3 (0.01)29 (0.13)

45 (0.21)

Arthritis

6 (0.03)6 (0.03)

Arthritis reactive

1 (0.00)

0

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Table 27. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30μg)(Na=21926)

Placebo(Na=21921)

nb (%)

nb (%)

15 (0.07)

23 (0.10)

01 (0.00)

Periarthritis

4 (0.02)

1 (0.00)

Polyarthritis

01 (0.00)

Rheumatoid arthritis

02 (0.01)

Spinal osteoarthritis

2 (0.01)

4 (0.02)

Spondylitis

1 (0.00)

1 (0.00)

Synovitis02 (0.01)1 (0.00)

4 (0.02)2 (0.01)2 (0.01)2 (0.01)2 (0.01)0

1 (0.00)

2 (0.01)1 (0.00)

2 (0.01)1 (0.00)

2 (0.01)1 (0.00)

SMQ

Overall SMQ
System Organ Class
Preferred Term
Osteoarthritis

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Patellofemoral pain syndrome

Temporomandibular joint syndrome
Convulsions (SMQ)

Any unsolicited adverse events within Convulsions(SMQ)
Nervous system disorders
Generalised tonic-clonic seizure
SeizureDemyelination (SMQ)

Any unsolicited adverse events within Demyelination(SMQ)
Nervous system disorders
Guillain-Barre syndrome01 (0.00)

2 (0.01)0

182 (0.83)

161 (0.73)

Ear and labyrinth disorders01 (0.00)

Allergic otitis media

01 (0.00)

Optic neuritis
Hypersensitivity (SMQ)

Any unsolicited adverse events within Hypersensitivity(SMQ)

Eye disorders

5 (0.02)5 (0.02)

Conjunctival oedema

01 (0.00)

Conjunctivitis allergic

3 (0.01)2 (0.01)0

1 (0.00)

Eye swelling0

1 (0.00)

Eyelid oedema

1 (0.00)

0

Swelling of eyelid

1 (0.00)

0

Gastrointestinal disorders

6 (0.03)3 (0.01)

Eye allergy

Gingival swelling0

1 (0.00)

Lip oedema

1 (0.00)

0

Lip swelling

2 (0.01)1 (0.00)

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Table 27. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30μg)(Na=21926)

Placebo(Na=21921)

nb (%)

nb (%)

Swollen tongue

2 (0.01)1 (0.00)

Tongue oedema

1 (0.00)08 (0.04)

9 (0.04)01 (0.00)

Face oedema

2 (0.01)0

Injection site dermatitis

1 (0.00)

0

Injection site rash

2 (0.01)1 (0.00)

Injection site urticaria

1 (0.00)

0

SMQ

Overall SMQ
System Organ Class
Preferred Term

General disorders and administration site conditions

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Application site rash

2 (0.01)7 (0.03)

Immune system disorders

Swelling face

10 (0.05)

13 (0.06)

Anaphylactic reaction

1 (0.00)

0

Anaphylactic shock0

1 (0.00)

Drug hypersensitivity

7 (0.03)7 (0.03)

Hypersensitivity

2 (0.01)5 (0.02)5 (0.02)

1 (0.00)

Infections and infestations

0

1 (0.00)

PustuleDermatitis infected

3 (0.01)0

Rash pustular

2 (0.01)0

3 (0.01)0

Administration related reaction

2 (0.01)0

Stoma site rash

1 (0.00)01 (0.00)01 (0.00)0

19 (0.09)

21 (0.10)

01 (0.00)

Injury, poisoning and procedural complications

Investigations
Blood immunoglobulin E increased
Respiratory, thoracic and mediastinal disorders
Allergic respiratory disease
Allergic sinusitis

2 (0.01)0

Bronchospasm

3 (0.01)3 (0.01)

Pharyngeal swelling

1 (0.00)

3 (0.01)

Rhinitis allergic

13 (0.06)

14 (0.06)

Skin and subcutaneous tissue disorders

134 (0.61)

119 (0.54)

Angioedema

3 (0.01)2 (0.01)

Dermatitis

5 (0.02)4 (0.02)

Dermatitis acneiform

1 (0.00)

0

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Table 27. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30μg)(Na=21926)

Placebo(Na=21921)

nb (%)

nb (%)

Dermatitis allergic

3 (0.01)5 (0.02)

Dermatitis atopic

01 (0.00)

SMQ

Overall SMQ
System Organ Class
Preferred Term

Dermatitis bullous

01 (0.00)

Dermatitis contact

14 (0.06)

21 (0.10)

Dermatitis exfoliative

1 (0.00)00

2 (0.01)

Eczema7 (0.03)3 (0.01)

Erythema nodosum

1 (0.00)

0

Fixed eruption

1 (0.00)

0

Hand dermatitis

2 (0.01)2 (0.01)

Perioral dermatitis

01 (0.00)

Pruritus allergic02 (0.01)Rash

62 (0.28)

52 (0.24)

Rash erythematous

2 (0.01)3 (0.01)

Rash maculo-papular

7 (0.03)4 (0.02)

Rash papular

1 (0.00)

0

Rash pruritic

8 (0.04)

6 (0.03)

Urticaria

18 (0.08)

15 (0.07)01 (0.00)

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Drug eruption

Urticaria contact
Urticaria papular
Peripheral neuropathy(SMQ)

Any unsolicited adverse events within Peripheral
neuropathy (SMQ)
Nervous system disorders
Guillain-Barre syndrome
Neuralgia
Neuritis

01 (0.00)

3 (0.01)

6 (0.03)3 (0.01)

6 (0.03)0

1 (0.00)

1 (0.00)

1 (0.00)01 (0.00)

Neuropathy peripheral

1 (0.00)

3 (0.01)

Peripheral sensory neuropathy

1 (0.00)

0

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Table 27. Selected Standard MedDRA Queries From Dose 1 to Unblinding Date –Blinded Placebo-Controlled Follow-up Period – Phase 2/3 Subjects ≥16
Years of Age – Safety Population
Vaccine Group (as Administered)

SMQ

Overall SMQ
System Organ Class
Preferred Term

BNT162b2 (30μg)(Na=21926)

Placebo(Na=21921)

nb (%)

nb (%)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For "any event," n = thenumber of subjects reporting at least 1 occurrence of any event.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 14APR2021(10:22)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA_RR/adae_smq_nzud_16_saf

2.7.4.2.4.3.4.2.1. Angioedema
Overall, the number and percentage of participants with any unsolicited AE within the SMQof angioedema were low and similar in the BNT162b2 group (30 [0.14%]) and placebo group(29 [0.13%]) (Table 27). AEs were most frequently reported in the SOC of skin andsubcutaneous tissue disorders (21 [0.10%] BNT162b2 vs 18 [0.08%] placebo) with urticaria
the most frequently reported PT.
In the SOC of gastrointestinal disorders within the SMQ of angioedema, lip edema, or lip
swelling was observed in 3 participants in the BNT162b2 group versus 1 participant in theplacebo group. Swollen tongue or tongue edema was observed in 3 participants in the
BNT162b2 group versus 1 participant in the placebo group. Lip swelling in 1 participant in
the BNT162b2 group and swollen tongue in 1 participant in the placebo group wereconsidered as related to the study intervention:In the BNT162b2 group, 1 participant experienced mild upper and lower lip swelling
14 and 19 days after Dose 1 which lasted 2 days before resolving and was considered
as related to the study intervention. This same participant also experienced upper lip
swelling and drug hypersensitivity 2 days after Dose 2, which wererecovering/resolving as of the data cutoff date and were considered related to study
intervention by the investigator.

In the placebo group, 1 participant experienced moderate swollen tongue as well as
moderate pharyngeal swelling 21 days after Dose 2; both resolved after 9 days; thisparticipant also experienced moderate drug hypersensitivity and mild rash (on chin,elbows, knees, neck and back) 2 days after Dose 2 which lasted for 28 days and 30

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days, respectively, and resolved. Swollen tongue as well as these other AEs were allconsidered related to the study intervention by the investigator.
Narratives for related angioedema SMQ events are provided (see Section 2.7.4.2.4.4). Referto the following participants:
Subject C4591001 1044 10441139
Subject C4591001 1111 11111099
Subject C4591001 1246 12461025
Subject C4591001 1005 10051214
Subject C4591001 1111 11111092
Subject C4591001 1027 10271105

Subject C4591001 1068 10681066
Subject C4591001 1090 10901507
Subject C4591001 1117 11171121
Subject C4591001 1091 10911274
Subject C4591001 1092 10921123
Subject C4591001 1140 11401035

Angioedema events in the other SMQs were all reported at low percentages in the BNT162b2(≤0.02) and placebo groups (≤0.03%) (Table 27).

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2.7.4.2.4.3.4.2.2. Arthritis
Overall, the number and percentage of participants with any unsolicited AE within the SMQ
of arthritis was lower in the BNT162b2 group (35 [0.16%]) than in placebo group(48 [0.22%]) (Table 27). AEs were most frequently reported within the SOC musculoskeletaland connective tissue disorders (0.13% BNT162b2 vs 0.21% placebo) with osteoarthritis themost frequently reported PT.
2.7.4.2.4.3.4.2.3. Convulsions
Overall, the number and percentage of participants with any unsolicited AE within the SMQof convulsions was low and equal in the BNT162b2 group and placebo group (2 participants[0.01%] in each group) (Table 27). All events were in the SOC of nervous system disorders:seizure (2 participants in the BNT162b2 group) and generalized tonic-clonic seizure (1participant in the placebo group).
2.7.4.2.4.3.4.2.4. Demyelination
Overall, the number and percentage of participants with any unsolicited AE within the SMQof demyelination was low: 2 (0.01%) participants in the BNT162b2 group and 1 (0.00%)
participant in the placebo group. All events were in the SOC of nervous system disorders.
Optic neuritis was observed in 2 participants in the BNT162b2 group and none in the placebogroup; 1 case occurring in a male participant and 1 case occurring in a female participant.
Both participants were in the younger age group. These events occurred 79 and 81 days after
their last vaccination of BNT162b2. Both were considered not related to BNT162b2. Bothevents were reported as SAEs. Narratives for optic neuritis cases (Subject C4591001 1008
10081152 and Subject C4591001 1231 12313028) are provided (see Section 2.7.4.2.4.4).
Guillain-Barre syndrome was reported as an SAE in 1 participant (Subject C4591001 1135
11351368) in the placebo group (see Section 2.7.4.2.4.4 regarding narrative).
These events of optic neuritis and Guillain-Barre syndrome are also included in safety
analyses by medical category (SMQ and SOC) in Section 2.7.4.2.4.3.4.3.
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2.7.4.2.4.3.4.2.5. Hypersensitivity
Overall, the number and percentage of participants with any unsolicited AE within the SMQof hypersensitivity was higher in the BNT162b2 group (182 [0.83%]) than in the placebogroup (161 [0.73%]) (Table 27).
The difference was mainly due to:Skin and subcutaneous tissue disorders (134 [0.61%] BNT162b2 vs 119 [0.54%] placebo):rash (62 [0.28%] BNT162b2 vs 52 [0.24%] placebo)rash maculo-papular (7 [0.03%] BNT162b2 vs 4 [0.02%] placebo)rash papular (1 [0.00%] BNT162b2 vs 0 placebo)

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Rash was assessed as related to study intervention at a higher IR in the BNT162b2 group(0.3) than in the placebo group (0.1).
In the SMQ of hypersensitivity in the SOC of infections and infestations: pustule and rashpustular were reported only in the BNT162b2 group by 3 (0.01%) and 2 (0.01%) participants,
respectively. In the SOC of injury, poisoning and procedural complications, administration
related reaction (2 participants) and stoma site rash (1 participant) were reported only in the
BNT162b2 group.
Additionally, in the SMQ of hypersensitivity in the SOC of gastrointestinal disorders, lipedema, lip swelling, swollen tongue, and tongue edema were observed more frequently in the
BNT162b2 group versus the placebo group. Refer to the Angioedema section(Section 2.7.4.2.4.3.4.2.1) for details.
Anaphylactic reaction was observed in 1 participant in the BNT162b2 group (refer to
Section 2.7.4.2.4.3.4.1.1 for more detail).
In the SMQ of hypersensitivity in the SOC of investigations, increased blood IgE wasobserved in 1 participant in the BNT162b2 group.
2.7.4.2.4.3.4.2.6. Peripheral Neuropathy
Overall, the number and percentage of participants with any unsolicited AE within the SMQ
of peripheral neuropathy was lower in the BNT162b2 group (3 [0.01%]) than in the placebogroup (6 [0.03%]). All PTs were in the SOC of nervous system disorders (Table 27).
2.7.4.2.4.3.4.3. Other Non-CDC Adverse Events of Special Interest – Select Standard
MedDRA Queries for COVID-19
Additional terms beyond those designated by the CDC as AESIs were evaluated to assess
potential imbalances between the BNT162b2 and placebo groups, and further characterized
such an imbalance. PTs associated with these AE categories and by SOC/PT were identified
during the blinded placebo-controlled follow-up period (Table 28). These events are
summarized below.
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Table 28. Incidence Rates of at Least 1 Adverse Event Category of Special Interest
From Dose 1 to Unblinding Date, by Adverse Event Category andPreferred Term – Blinded Placebo-Controlled Follow-up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
Adverse Event Category
Preferred Termnc

Placebo(Na=21921, TEb=82.2)

DifferenceIR(95% CIe) nc
IR(95% CIe)
IRD(/100 PY)d(/100 PY)d(/100 PY)f

(95% CIg)

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ACUTE MYOCARDIAL
INFARCTION
Acute coronary syndrome

1

0.0(0.0, 0.1)

4

0.0

(0.0, 0.1)

-0.04(-0.09, 0.02)

Acute myocardial infarction

6

0.1(0.0, 0.2)

4

0.0

(0.0, 0.1)

0.02(-0.05, 0.10)

Coronary artery occlusion

00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Myocardial infarction

4

0.0(0.0, 0.1)

8

0.1

(0.0, 0.2)

-0.05(-0.13, 0.03)

Anaphylactic reaction

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Anaphylactic shock0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Appendicitis

14

0.2

(0.1, 0.3)

9

0.1

(0.1, 0.2)

0.06(-0.06, 0.17)

Appendicitis perforated

1

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

-0.00(-0.03, 0.03)

Complicated appendicitis

00.0(0.0, 0.0)2

0.0

(0.0, 0.1)

-0.02(-0.06, 0.01)

Arthralgia

281

3.4

(3.0, 3.8) 122

1.5(1.2, 1.8)

1.88

(1.41, 2.36)

Arthritis

60.1(0.0, 0.2)

6

0.1

(0.0, 0.2)

-0.00(-0.08, 0.08)

Arthritis reactive

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Facial paralysis

40.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.04(-0.02, 0.09)

Facial paresis

00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

COVID-190

0.0(0.0, 0.0)

13

0.2

(0.1, 0.3)

-0.16(-0.24, -0.07)

COVID-19 pneumonia

1

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

-0.00(-0.03, 0.03)

0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Toxic encephalopathy

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Uraemic encephalopathy

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

ANAPHYLAXISAPPENDICITISARTHRITIS/ARTHRALGIA

BELL’S PALSY

COVID-19 DISEASE

DEATH
Death
ENCEPHALOPATHYGUILLAIN-BARRE SYNDROME
Guillain-Barre syndrome

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Table 28. Incidence Rates of at Least 1 Adverse Event Category of Special Interest
From Dose 1 to Unblinding Date, by Adverse Event Category andPreferred Term – Blinded Placebo-Controlled Follow-up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)
Adverse Event Category
Preferred Termnc

Placebo(Na=21921, TEb=82.2)

DifferenceIR(95% CIe) nc
IR(95% CIe)
IRD(/100 PY)d(/100 PY)d(/100 PY)f

(95% CIg)

MULTISYSTEMINFLAMMATORY SYNDROME
IN CHILDREN (MIS-C) AND IN
ADULTS (MIS-A)
Multiple organ dysfunction
syndrome00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Angioedema

30.0(0.0, 0.1)

2

0.0

(0.0, 0.1)

0.01(-0.04, 0.06)

Hypersensitivity

20.0(0.0, 0.1)

5

0.1

(0.0, 0.1)

-0.04(-0.10, 0.03)

Lip swelling2

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.01(-0.03, 0.05)

Pruritus

24

0.3(0.2, 0.4)

20

0.2

(0.1, 0.4)

0.04(-0.11, 0.20)

Rash

62

0.7

(0.6, 1.0)

52

0.6

(0.5, 0.8)

0.11(-0.14, 0.36)

Rash pruritic

8

0.1(0.0, 0.2)

6

0.1

(0.0, 0.2)

0.02(-0.07, 0.11)

Swelling face

20.0

(0.0, 0.1)

7

0.1

(0.0, 0.2)

-0.06(-0.13, 0.01)

Swollen tongue

20.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.01(-0.03, 0.05)

Urticaria

18

0.2(0.1, 0.3)

15

0.2

(0.1, 0.3)

0.03(-0.10, 0.17)

2

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.02(-0.01, 0.06)

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

8

0.1(0.0, 0.2)

8

0.1

(0.0, 0.2)

-0.00(-0.10, 0.09)

Generalised tonic-clonic seizure00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Seizure2

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.01(-0.03, 0.05)

Haemorrhagic stroke00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Intraventricular haemorrhage0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Subarachnoid haemorrhage

4

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.04(-0.02, 0.09)

MYOCARDITIS

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Myocarditis
NON-ANAPHYLACTIC
ALLERGIC REACTIONSOPTIC NEURITIS
Optic neuritis
PERICARDITIS
Pericarditis
PULMONARY EMBOLISM
Pulmonary embolism
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Table 28. Incidence Rates of at Least 1 Adverse Event Category of Special Interest
From Dose 1 to Unblinding Date, by Adverse Event Category andPreferred Term – Blinded Placebo-Controlled Follow-up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)

Placebo(Na=21921, TEb=82.2)

Difference

Adverse Event Category
Preferred TermncIR
(95% CIe) nc
IR(95% CIe)
IRD(/100 PY)d(/100 PY)d(/100 PY)f

(95% CIg)

Cerebellar infarction

0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Cerebral infarction

0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Cerebrovascular accident

4

0.0(0.0, 0.1)

1

0.0

(0.0, 0.1)

0.04(-0.02, 0.09)

Ischaemic stroke

20.0(0.0, 0.1)

2

0.0

(0.0, 0.1)

-0.00(-0.05, 0.05)

Transient ischaemic attack

2

0.0(0.0, 0.1)

3

0.0

(0.0, 0.1)

-0.01(-0.07, 0.04)

Platelet count decreased

10.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Thrombocytopenia

1

0.0(0.0, 0.1)

2

0.0

(0.0, 0.1)

-0.01(-0.05, 0.03)

Abortion incomplete00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Abortion spontaneous

20.0(0.0, 0.1)

3

0.0

(0.0, 0.1)

-0.01(-0.07, 0.04)

Abortion spontaneous incomplete00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Exposure during pregnancy

30

0.4

(0.2, 0.5)

42

0.5

(0.4, 0.7)

-0.15(-0.35, 0.05)

Retained products of conception0

0.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Coagulopathy

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Deep vein thrombosis

7

0.1(0.0, 0.2)

7

0.1

(0.0, 0.2)

-0.00(-0.09, 0.09)

Ophthalmic vein thrombosis

1

0.0(0.0, 0.1)0

0.0

(0.0, 0.0)

0.01(-0.01, 0.04)

Penile vein thrombosis

00.0(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

Venous thrombosis limb

0

0.0

(0.0, 0.0)1

0.0

(0.0, 0.1)

-0.01(-0.04, 0.01)

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THROMBOCYTOPENIAVACCINATION DURING
PREGNANCY AND ADVERSEPREGNANCY OUTCOMESVENOUS THROMBOEMBOLISMCONFIDENTIAL
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Table 28. Incidence Rates of at Least 1 Adverse Event Category of Special Interest
From Dose 1 to Unblinding Date, by Adverse Event Category andPreferred Term – Blinded Placebo-Controlled Follow-up Period – Phase
2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=21926, TEb=83.4)

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Adverse Event Category
Preferred Termnc

Placebo(Na=21921, TEb=82.2)

DifferenceIR(95% CIe) nc
IR(95% CIe)
IRD(/100 PY)d(/100 PY)d(/100 PY)f

(95% CIg)

Note: MedDRA (v23.1) coding dictionary applied.
Note: The 95% confidence interval quantifies the precision of the incidence rate difference estimate. Confidence intervals
are not adjusted for multiplicity. They should only be used to identify potentially important adverse events.
a. N = number of subjects in the specified group.
b. TE = total exposure time in 100 person-years across all subjects in the specified group. Exposure time for a subject isthe time from Dose 1 to the end of blinded follow-up. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person-years(PY) across all subjects in the specified group.
e. 2-sided CI based on Poisson distribution.
f. Difference in incidence rate (BNT162b2 [30 μg] - placebo).
g. 2-sided Wald CI for the incidence rate difference.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (20:15) Source Data: adae Table Generation: 16APR2021(13:49)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA1/adae s131 aesi cat p3 saf

Acute Myocardial Infarction
Acute myocardial infarctions were searched with the PTs of acute myocardial infarction,acute coronary syndrome, coronary artery occlusion, and myocardial infarction. A total of
6 acute myocardial infarctions, 4 myocardial infarctions and 1 acute coronary syndrome(total of 11 events) were identified in the BNT162b2 group, and 4 acute myocardial
infarctions, 8 myocardial infarctions, 4 acute coronary syndrome, and 1 coronary artery
occlusion in the placebo group (total of 17 events), respectively. Slightly more than half ofthese events had onset distant to (ie, >30 days following) receipt of vaccine or placebo . Noneof these events were assessed by the investigator as related to study intervention . Outcome
was resolved in all participants in the BNT162b2 group; outcome in the placebo group was
fatal in 2 and resolved in the other participants.
Anaphylaxis
Overall, the category of anaphylaxis included 1 participant with anaphylactic reaction in the
BNT162b2 group and 1 participant with anaphylactic shock in the placebo group. These
events are further described in Section 2.7.4.2.4.3.4.1.1.
Appendicitis
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Overall, the category of appendicitis (including appendicitis perforated and complicatedappendicitis) included 15 participants in the BNT162b2 group and 12 participants in theplacebo group. These events are further described in Section 2.7.4.2.4.3.4.1.4.
Arthritis/Arthralgia
Arthralgia not associated with reactogenicity was evaluated starting from Day 8 after either
dose of BNT162b2. The IR of arthralgia assessed from Day 8 (ie, beyond the 7-dayreactogenicity period in which arthralgia is recorded in e-dairies for the reactogenicity
subset) after each dose was lower in the BNT162b2 group (0.6) than in the placebogroup (0.8).
Autoimmune Disease

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There are no search term SMQ that would reliably capture all potential autoimmune diseases.
Hence a comprehensive manual medical review of all reported AEs in the blinded placebocontrolled period was undertaken to identify PTs potentially indicative of autoimmune
disease. These PTs are summarized by vaccine group.
In the BNT162b2 group there were 10 autoimmune disease cases identified. There were 1
case each in the BNT162b2 group: autoimmune thyroiditis, ulcerative colitis, Crohn’sdisease, reactive arthritis, fibromyalgia, systemic lupus erythematosus, alopecia areata,
psoriasis, and 2 cases of psoriatic arthropathy.
In the placebo group there were 15 autoimmune cases identified. There were 1 case each inthe placebo group: autoimmune thyroiditis, celiac disease, alopecia areata, psoriasis,
Raynaud’s phenomenon, and 2 cases of psoriatic arthropathy, 2 cases of psoriasis, 2 cases ofulcerative colitis, 2 cases of rheumatoid arthritis, 3 cases of fibromyalgia.
Bell’s Palsy/Facial Paralysis
Overall, the category of Bell’s Palsy (facial paralysis and facial paresis) included
4 participants in the BNT162b2 group and 2 participants in the placebo group. These eventsare further described in Section 2.7.4.2.4.3.4.1.2.
Multiple Cases of COVID-19
There were 5 participants, all randomized to placebo, who developed 2 separate andclinically symptomatic instances of COVID-19 confirmed by NAAT at the central
laboratory. All of the second confirmed COVID-19 cases occurred during the period before
their first dose of BNT162b2 except for 1 participant (Subject 12211002) who developed his
second COVID-19 diagnosis 4 days after his second dose of BNT162b2. All participants
were N binding antibody negative prior to their first instance of COVID-19. The timeinterval between the first and second COVID-19 episode varied from 1 to 5 months.
Narratives for these cases are provided in Module 5.3.5.1 C4591001 6-Month Update Interim
CSR Section 14 COVID-19 Case (Severe and/or Multiple).

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Death
One death in the placebo group was captured as a potential AESI as there was no reported
primary cause of death at the time of the data cutoff. A narrative is provided (seeSection 2.7.4.2.4.4 [Subject C4591001 1152 11521085]). This death is also captured inTable 16 in the analysis of deaths reported from Dose 1 to the unblinding date
(Section 2.7.4.2.4.3.1).
Encephalopathy
Overall, the category of encephalopathy included 2 participants in the BNT162b2 group andnone in the placebo group. One participant reported an SAE of toxic encephalopathy 64 days
after Dose 2 in the setting of diverticulosis and a urinary tract infection, which resolved
8 days later, and the other participant reported an SAE of uraemic encephalopathy 36 days
after Dose 2, which resolved 3 days later. Both events were assessed by the investigator as
not related to study intervention.

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Guillain-Barre Syndrome
One participant in the placebo group reported an SAE of Guillain-Barre syndrome. This case
was also captured as a CDC AESI in Section 2.7.4.2.4.3.4.2.
Multisystem Inflammatory Syndrome
One participant in the placebo group reported an SAE of multiple organ dysfunction
syndrome.
Myocarditis
One case in the placebo group was reported.
Non-Anaphylactic Allergic Reactions
Overall, there was no imbalance in each of the PTs in non-anaphylactic allergic reactions(123 in the BNT162b2 group and 109 in the placebo group) (Table 28). Selected events arealso captured as CDC AESIs under SMQ of Angioedema and Hypersensitivity in
Section 2.7.4.2.4.3.4.2.
Optic Neuritis
Two participants in the BNT162b2 group reported an SAE each of optic neuritis. This case
was also captured as a CDC AESI in Section 2.7.4.2.4.3.4.2.
Pericarditis
There was 1 participant in the older BNT162b2 age group with pericarditis. The event had an
onset of 28 days after Dose 2, was ongoing at the data cutoff date, and was assessed by the

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investigator as not related to the study intervention. A narrative for this event is provided (seeSection 2.7.4.2.4.4 [Subject C4591001 1231 12315632]).
Pulmonary Embolism
PTs associated with pulmonary embolism were searched in the blinded placebo-controlled
period: Pulmonary embolism, Pulmonary thrombosis, Pulmonary venous thrombosis, andPulmonary artery thrombosis. There were 8 cases of pulmonary embolism in the BNT162b2
group and 8 cases in the placebo group.
Stroke, Hemorrhagic

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PTs associated with hemorrhagic stroke were searched in the blinded placebo-controlled
follow-up period: Haemorrhagic stroke, Cerebral haemorrhage, Haemorrhagic cerebral
infarction, Basal ganglia haemorrhage, Brain stem haemorrhage, Cerebellar haemorrhage,
subarachnoid hemorrrhage, and Intraventricular hemorrhage.
Overall, there were 4 hemorraghic strokes in the BNT162b2 and 3 in the placebo group. In
the BNt162b2 group there were 4 subarachnoid haemorrhages and in the placebo group therewas 1 subarachnoid haemorrhage, 1 intraventricular haemorrhage, and 1 haemorrhagic stroke(Table 28). Narratives for these events are provided (see Section 2.7.4.2.4.4). Refer to thefollowing participants:
Subject C4591001 1111 11111130
Subject C4591001 1226 12261571
Subject C4591001 1042 10421166
Subject C4591001 1054 10541173

Subject C4591001 1156 11561001
Subject C4591001 1090 10901175
Subject C4591001 1231 12313972

Stroke, Ischemic
PTs associated with ischemic stroke were searched in the blinded placebo-controlled followup period: Ischaemic stroke, Ischaemic cerebral infarction, Cerebral infarction, Lacunar
infarction, Cerebral ischaemia, Cerebellar stroke, Brain stem stroke, Vertebrobasilar stroke,
Embolic stroke, Thrombotic stroke, Thrombotic and cerebral infarction, Cerebral vascular
accident, transient ischemic attack, and Cerebellelar infarction.
There are a total of 8 of these PTs in the BNt162b2 group and 8 in the placebo group. There
were 2 ischemic strokes, 4 cerebral vascular accidents, 2 transient ischemic attacks identified
in the BNT162b2 group. In the placebo group there are 2 ischemic strokes, 3 transientischemic attacks, 1 cerebral vascular accident, 1 cerebral infarction and 1 cerebellar
infarction.
Thrombocytopenia
PTs associated with thrombocytopenia were searched in the blinded placebo-controlled
period and included Thrombocytopenia and platelet count decreased. The BNT162b2 group

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had 1 case of thrombocytopenia and 1 case of platelet count decreased, and the placebo grouphad 2 cases of thrombocytopenia.
Vaccination During Pregancy and Pregnancy Outcomes
There was no imbalance between the BNT162b2 group versus the placebo group with regard
to pregnancy and maternal exposure. Pregnancy and maternal exposure reported during thestudy is discussed in Section 2.7.4.2.4.3.6.2. Narratives for these events are provided (seeSection 2.7.4.2.4.4).
Venous Thromboembolism

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PTs associated with venous thromboembolism were searched in the blinded placebocontrolled period: Cerebral venous sinus thrombosis, Cerebral venous thrombosis, Cerebral
thrombosis, Superior sagittal sinus thrombosis, Deep vein thrombosis, Venous thrombosis
limb, Retinal vein thrombosis, Retinal vein occlusion, Mesenteric vein thrombosis,
Thrombosis mesenteric vessel, Splenic thrombosis, Splenic vein thrombosis, Splenic
embolism, Visceral venous thrombosis, Hepatic vein thrombosis, Hepatic vein embolism,
Vena cava thrombosis, Vena cava embolism, Renal vein thrombosis, Renal vein embolism,
Venous thrombosis, Thrombosis, Embolism, and Thrombotic microangiopathy.
Overall, there were 9 thrombotic events in the BNT162b2 group and 9 in the placebo group.
In the BNT162b2 group included 7 deep vein thromboses, 1 coagulopathy, and 1 ophthalmicvein thrombosis and in the placebo group included 7 deep vein thromboses, 1 penile veinthrombosis, and 1 venous thrombosis limb (Table 28) . None of the venous events wereassociated with thrombocytopenia.
2.7.4.2.4.3.4.4. Narratives of Other Significant Adverse Events (Phase 3, Study
C4591001)
Narratives of other significant AEs for Phase 3 participants through the data cutoff date
(13 March 2021) are provided (see Section 2.7.4.2.4.4).
2.7.4.2.4.3.5. Analysis of Adverse Events by Organ System or Syndrome (Phase 3, Study
C4591001)
Safety data from Phase 3 of Study C4591001 were reviewed and Adverse Reactions (ADRs)– adverse events for which there is reason to conclude that the vaccine caused the event were identified. The review included AE data, as well as local reactions and systemic events
collected systematically by e-diaries. The CIOMS frequency categories for adverse reactions
are as follows:






Very common: ≥10%
Common: ≥1% and <10%Uncommon: ≥0.1% and <1%
Rare: ≥0.01% and <0.1%
Very rare: <0.01%

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Reactogenicity ADRs that occurred with a very common frequency, based on any dose in the
BNT162b2 group, from the reactogenicity subset of data as of 13 March 2021, are:









Injection site pain: 4153/4924 (84.3%)
Fatigue: 3185/4924 (64.7%)
Headache: 2814/4924 (57.1%)
Muscle pain: 1980/4924 (40.2%)
Chills: 1707/4924 (34.7%)
Joint pain: 1232/4924 (25.0%)
Fever: 749/4924 (15.2%)
Injection site swelling: 546/4924 (11.1%)

A reactogenicity ADR that occurred with a common frequency, based on any dose in the
BNT162b2 group from the reactogenicity subset of data as of 13 March 2021, was injection
site redness:

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Injection site redness: 486/4924 (9.9%)

ADRs considered as common (nausea) and uncommon (lymphadenopathy and malaise) inthe BNT162b2 group were identified from AE data in the safety population as of 13 March
2021, compared to placebo for reference:Nausea: 274/21,926 (1.2%) in the BNT162b2 group vs 87/21,921 (0.4%) in theplacebo group



Lymphadenopathy: 83/21,926 (0.4%) in the BNT162b2 group vs 7/21,921 (0.0%) in
the placebo group

Malaise: 130/21,926 (0.6%) in the BNT162b2 group vs 22/21,921 (0.1%) in theplacebo group

The following additional ADRs were identified in the post-authorization setting. Frequencies
for these ADRs were obtained from clinical trial data (Study C4591001) when possible, as
per labeling guidance.









Diarrhea (very common)
Vomiting (common)
Pain in Extremity (uncommon)
Rash (uncommon)
Pruritus (uncommon)
Urticaria (uncommon)
Angioedema (rare)
Anaphylaxis (unknown)

It should be noted that at the time of conditional approval of BNT162b2 by EMA, thesponsor was asked to include the following as ADRs in the SmPC even though they were not
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considered ADRs in the Core Data Sheet (CDS). The frequencies in the initial EMAapproved SmPC reflected data from the initial conditional approval submission (data cutoff
date: 14 November 2020):


Acute peripheral facial paralysis 3/18801 = 0.02% (rare)
Injection site pruritus 27/18801 = 0.1% (uncommon)
Insomnia 23/18801 = 0.1% (uncommon)

The following ADRs have been identified from the clinical study data and are supported byreports in the post-authorization setting. The CIOMS frequency category for these reactions
is uncommon (based on clinical trial data [Study C4591001]): lethargy, asthenia, decreased
appetite, hyperhidrosis, and night sweats. These ADRs will be added to the CDS andsubsequently proposed for all BNT162b2 labels. The additional ADRs further characterize
the safety profile of BNT162b2 but do not impact its favorable risk:benefit profile.
2.7.4.2.4.3.6. Other Safety Assessments (Phase 3, Study C4591001)

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2.7.4.2.4.3.6.1. Severe COVID-19 Illness (Phase 3, Study C4591001)
The protocol had prespecified stopping rules that included monitoring of severe COVID-19
cases, and these stopping criteria were not met. The confinement of the majority of severecases to the placebo groups suggests no evidence for vaccine-associated enhanced disease(VAED) including vaccine-associated enhanced respiratory disease (VAERD).
A description of severe COVID-19 cases evaluated for efficacy in Phase 2/3 is presented in
Sections 11.1.1.3 and 11.1.2.3.2 of the final analysis interim CSR (Module 5.3.5.1 C4591001
Efficacy Final Analysis Interim CSR). A description of severe COVID-19 cases in the
updated analysis of efficacy in Phase 2/3 is presented in Section 11.1.2.2.1 of the 6-Month
Update CSR (Module 5.3.5.1 C4591001 6-Month Update CSR).
2.7.4.2.4.3.6.2. Pregnancy (Phase 3, Study C4591001)
At the time of the data cutoff date (13 March 2021), a total of 50 participants who hadreceived BNT162b2 had reported pregnancies, including 42 participants originallyrandomized to the BNT162b2 group and 8 participants originally randomized to the placebogroup who then received BNT162b2. In total, 12 participants (n=6 each in the randomized
BNT162b2 and placebo groups) withdrew from the blinded placebo-controlled vaccination
period of the study due to pregnancy, and 4 participants originally randomized to placebo
who then received BNT162b2 withdrew from the open-label vaccination period due topregnancy (Table 31). These participants continue to be followed for pregnancy outcomes.
Narratives for participants who reported a pregnancy during the study, including any reported
outcomes, are provided (see Section 2.7.4.2.4.4).
2.7.4.2.4.4. Narratives (Phase 3, Study C4591001)
Narratives for Phase 3 participants (including for deaths, SAEs, AEs leading to withdrawal,
other significant AEs, COVID-19 cases, and pregnancies) are provided in Module 5.3.5.1
C4591001 6-Month Update Interim CSR Section 14.
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2.7.4.2.4.5. Conclusions (Phase 3, Study C4591001)
Based on Phase 2/3 data from approximately 44,000 participants ≥16 years of age with up toat least 6 months of follow-up after Dose 2 in Study C4591001, BNT162b2 at 30 µg was safe
and well-tolerated across age groups. Reactogenicity AEs were generally milder and lessfrequent in participants in the older group (>55 years of age) compared with the younger
group (≤55 years of age). Reactogenicity was mostly mild to moderate and short-lived after
dosing for both younger and older age groups (ie, median onset between 1 to 3 days after
dosing and resolution within 1 to 2 days after onset). The incidence of SAEs and deaths were
low in the context of the number of participants enrolled and comparable between
BNT162b2 and placebo. The incidence of discontinuations due to AEs was also generally
low and similar between BNT162b2 and placebo groups.
Cumulative safety follow-up to at least 6 months after Dose 2 for approximately 12,000
Phase 2/3 participants originally randomized to BNT162b2, comprising the combined
blinded and open-label periods, showed no new safety signals or suggested any new safetyconcerns arising from longer-term follow-up.

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Similarly, open-label follow-up of participants originally randomized to placebo from thetime of unblinding to receive BNT162b2 until the data cutoff date showed no new safety
signals or concerns.
Safety analysis results for subgroups based on demographics (age, race, ethnicity) and bybaseline SARS-CoV-2 positive versus negative status have not shown any clinicallyimportant differences in the BNT162b2 safety profile. Analysis of the subset of individuals
with stable HIV did not suggest any safety concerns in this population. Analysis ofparticipants originally randomized to placebo who then received BNT162b2 (Dose 3) bydemographic subgroups and based on prior evidence of SARS-CoV-2 infection or prior
COVID-19 did not suggest any safety concerns.
Phase 2/3 safety data were generally concordant with safety data in Phase 1 of the study, bothoverall and with regard to younger and older participants.
2.7.4.2.5. Discussion
Safety data in the Phase 1 BNT162b2 30 µg groups of younger and older adults, evaluated up
to approximately 6 months after Dose 2, continue to support the safety and tolerability profile
of BNT162b2.
In the Phase 2/3 portion of the study, safety data in participants ≥16 years of age are available
for ~44,000 participants, of which ~12,000 had a total exposure time of ≥6 months after
Dose 2 of BNT162b2 at the time of the data cutoff date (13 March 2021). The prompted local
and systemic reactogenicity profile was consistent with results previously reported in the
final analysis interim C4591001 CSR dated 03 December 2020. Increases in systemic
reactogenicity were observed after Dose 2 compared with after Dose 1. Older adults
generally reported milder and lower frequencies of local and systemic reactogenicity events
compared with younger adults. Most prompted local and systemic reactogenicity eventswere short-lived, and only 1 Grade 4 event of fever lasting 1 day was reported. Median onset
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day for most local and systemic reactions occurred within the first 3 days following
vaccination and resolved with median durations within 3 days without sequela. This patternof reactogenicity is also observed in participants with stable HIV infection.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)The Phase 2/3 AE profile of BNT162b2 at 30 µg was also consistent with results previously
reported in the final analysis interim C4591001 CSR dated 03 December 2020. During theblinded placebo-controlled follow-up period, AEs from Dose 1 to 1 month after Dose 2 andfrom Dose 1 to the unblinding date of AEs were mostly mild or moderate with higher
frequencies/IRs in the BNT162b2 group than in the placebo group. Since many AEs were in
SOCs that contain AEs consistent with reactogenicity events, an analysis of AEs within
7 days after each dose showed that the AEs during this time period in the BNT162b2 groupwere largely attributed to reactogenicity events. For participants who did not have an
e-diary, they reported their experience as AEs. As such they were not prompted to reportspecific terms within 7 days after either dose. The analysis of AEs reported in the placebocontrolled period of the study identified several terms that are reported more frequently in thevaccine group than placebo. These include pain in the extremity, decreased appetite, lethargy,
asthenia, malaise, night sweats and hyperhidrosis. The majority of the events started soonafter vaccination and for most of these events the rates were higher after Dose 2 than Dose 1.
This suggest that these terms describe the participants’ unprompted experience ofreactogenicity within 7 days after each dose.
Cumulative safety data for 12,006 Phase 2/3 participants with at least 6 months follow-up
after Dose 2 for participants originally randomized to BNT162b2, comprising the combined
blinded and open-label periods, showed no new safety signals arising from longer-term
follow-up. Importantly, the additional follow-up time allowed for more opportunity to collectSAEs. However, related SAEs did not increase during this time period and it remained verylow.
Similarly, open-label observational follow-up of original BNT162b2 participants after
unblinding and original placebo participants who then received BNT162b2 after unblinding
showed no new safety signals or concerns.
CDC-defined AESIs were evaluated in the blinded placebo-controlled follow-up period.
MedDRA search terms were used to identify AE that fit the medical concept and then the
resultant events were evaluated for numerical imbalances where the events were higher in thevaccine group than placebo and then narratives were provide only for those AESIs with thenumerical imbalance.
The analysis showed that most AESI are reported in higher numbers in the placebo group or
were equal between vaccine and placebo. The allergic reactions evaluation did not identify
anaphylactic reactions associated with the vaccine. Note, there was an anaphylactoid reaction
reported 2 days after receiving open-label BNT162b2 (Dose 3) in an originally placeborandomized participant who was unblinded to receive BNT162b2, and who had a significant
ongoing medical history of drug hypersensitivity and other allergies. For angioedema thefrequencies were low and very similar in the BNT162b2 (0.14%) and placebo (0.13%)
groups. For hypersensitivity reactions most of the reactions were due to rash, rash maculopapular, and rash papular and were not reported within 7 days after either dose. Overall, the
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evaluation of cases reporting allergic reactions supports standard precautions for allergic
reactions should be taken in the clinic when vaccinating.
There were 2 cases of optic neuritis reported in the vaccine group that occurred 79 and81 days after vaccination with BNT162b2. Both were considered not related to vaccine.
Given the few number of events, non-proximity to vaccination and investigators judgment,
there is not enough information to assess causality at this time.

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)AESI evaluations were performed for blinded placebo-controlled follow-up. There were 4
cases of Bell’s palsy reported in the BNT162b2 group (previously reported in the final
analysis interim C4591001 CSR dated 03 December 2020). Since then there have been 2
additional cases in the placebo group during blinded placebo-controlled follow-up, and there
have been 4 additional cases of Bell’s palsy identified during the open-label follow up periodthat are included for completeness: 3 cases in placebo participants who became unblinded
and were then vaccinated with BNT162b2, and 1 participant who was originally randomized
to BNT162b2, was unblinded, and developed Bell’s palsy 154 days after the second dose of
BNT162b2.
There were 2 cases of encephalopathy in the vaccine group and none in the placebo. Bothcases had clear etiologic causes (uremia and toxic encephalopathy after a fall withhypotension, diverticulum, and a urinary tract infection) and hence are not associated withthe vaccine.
SAEs assessed by the investigator as related to study intervention were:

5 SAEs total during blinded placebo-controlled follow-up: 3 SAEs
(lymphadenopathy, shoulder injury related to vaccine administration [SIRVA], andventricular arrhythmia) in the BNT162b2 group from Dose 1 to 1 month after Dose 2,
and 2 SAEs (paraesthesia [BNT162b2 group] and psoriatic arthropathy [placebo]) to
the unblinding date.



2 SAEs total during open-label follow-up: 1 SAE of myocardial infarction in
1 original BNT162b2 participant and 1 SAE of anaphylactoid reaction in 1 originalplacebo participant who then received BNT162b2.

During blinded placebo-controlled follow-up, there were a total of 15 deaths in the
BNT162b2 group and 14 deaths in the placebo group, with 3 and 5 deaths occurring from
Dose 1 to 1 month after Dose 2 in the BNT162b2 and placebo groups, respectively. Of these,
there were 2 deaths in participants (1 BNT162b2 and 1 placebo) with confirmed stable HIV
disease.
During the open-label follow-up period, there were 3 deaths in original BNT162b2
participants and 2 deaths in original placebo participants who then received BNT162b2.
None of the deaths were assessed by the investigator as related to study intervention.
Subgroup analyses by baseline SARS-CoV-2 status, ethnicity, race, and sex did not reveal
any clinically meaningful differences in safety results. Analysis of participants originally
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randomized to placebo who then received BNT162b2 (Dose 3) by demographic subgroups
and based on prior evidence of SARS-CoV-2 infection or prior COVID-19 did not suggest
any safety concerns. Importantly, there were 5 cases of individuals randomized to placebo
who developed COVID-19 twice (ie, a new clinical episode with different symptoms andseparated by at least a month apart confirmed by NAAT by the central laboratory). Each ofthese participants received BNT162b2 after unblinding without reported safety events. Taken
together individuals who had evidence of infection with SARS-CoV-2 at baseline ordeveloped COVID-19 once or twice before receiving BNT162b2 tolerated the vaccine well.
Overall, the available evidence up to 6 months of follow-up from the Phase 2/3 pivotal study
continues to support the safety and tolerability of BNT162b2 at 30 µg administered as a 2dose regimen (21 days apart) to individuals ≥16 years of age for the prevention of
COVID-19.
2.7.4.3. Safety in Special Groups and Situations
2.7.4.3.1. Intrinsic Factors
2.7.4.3.1.1. Geriatric Use

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Clinical studies of BNT162b2 (30 µg) include participants 65 years of age and older and theirdata contributes to the overall assessment of safety and efficacy.
The ongoing pivotal Study C4591001 has enrolled participant groups >65 years of age as anolder 65-85 years of age cohort during the Phase 1 dose-finding portion of the study and inthe >55 years of age stratum in the larger Phase 2/3 portion of the study. Safety data analyses
have described the clinical outcomes for these older adults in the Phase 1 portion of the study(Section 2.7.4.2.2), which was subsequently confirmed in the Phase 2 portion of the study(Section 2.7.4.2.3), joined by pivotal safety data including older adults in Phase 3(Section 2.7.4.2.4).
Descriptive differences between older and younger adults have been observed in all phases;
namely, that older adults tend to have milder and less frequent reactogenicity events, which
are generally known to be commonly age-related. Overall, available clinical data demonstrate
a predominantly mild reactogenicity profile in older adults.
At the time of this application, vaccine safety in elderly individuals is evident from thetotality of clinical safety data.
2.7.4.3.1.2. Pediatric Use
Further study of pediatric use of the vaccine and/or immunobridging study will be
undertaken to characterize the vaccine response in children.
2.7.4.3.1.3. Use in Immunocompromised Individuals
Individuals who are immunocompromised or taking immunosuppressive therapy at the timeof vaccine administration may have diminished response to immunization. Pivotal Study
C4591001 included enrollment of individuals with medical history of immunocompromised

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medical condition or immunosuppressive therapy (Section 2.7.4.1.1.2.3). There are limited
data on the safety of the vaccine in this patient population at the time of this application.
2.7.4.3.2. Extrinsic Factors
Not applicable.
2.7.4.3.3. Drug Interactions
Refer to Module 5.3.5.1 C4591001 Protocol Section 6.5 for details regarding prior andconcomitant vaccines, medications and procedures that were allowed or prohibited.
2.7.4.3.4. Use in Pregnancy and Lactation
Study BNT162-01
There were no pregnancies reported through the data cutoff date of 13 August 2020.

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Study C4591001
Women who were pregnant or breastfeeding were not eligible to participate inStudy C4591001 (Section 2.7.4.1.1.2.3). At the time of the most recent data cutoff in Study
C4591001 (13 March 2021), a total of 50 participants had reported pregnancies in the safety
database. Further details are provided in Section 2.7.4.2.4.3.6.2. These participants continue
to be followed for pregnancy outcomes.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. Available data on
BNT162b2 administered to pregnant women are insufficient to inform vaccine-associatedrisks in pregnancy. In a DART study, no vaccine-related adverse effects on female fertility,
fetal development, or postnatal development were reported.
The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for vaccination with BNT162b2 and any potential adverse effects on
the breastfed child from BNT162b2 or from the underlying maternal condition. For
preventive vaccines, the underlying maternal condition is susceptibility to disease prevented
by the vaccine.
Narratives for pregnancy are provided (Section 2.7.4.2.4.3.6).
2.7.4.3.5. Overdose
In Study C4591001, any dose of study intervention greater than 30 µg within a 24-hour time
period was considered an overdose (refer to Module 5.3.5.1 C4591001 Protocol Section 8.4
for more information). An error in dilution during the study resulted in 52 participantsreceiving a higher than intended dose of BNT162b2; instead of receiving 30 µg of
BNT162b2, 58 µg of BNT162b2 was administered. The participants did not report anincrease in reactogenicity or adverse events.
2.7.4.3.6. Drug Abuse
Not applicable.
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2.7.4.3.7. Withdrawal and ReboundNot applicable.
2.7.4.3.8. Effects on Ability to Drive or Operate Machinery or Impairment of Mental
Ability
BNT162b2 has no or negligible influence on the ability to drive and use machines.
2.7.4.4. Post-Authorization Data

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Post-authorization safety data are continually monitored by Pfizer and BioNTech forpharmacovigilance and risk management purposes. Pfizer’s safety database contains cases of
AEs reported spontaneously to Pfizer, cases reported by the health authorities, cases
published in the medical literature, cases from Pfizer-sponsored marketing programs, noninterventional studies, and cases of serious AEs reported from clinical studies regardless of
causality assessment. Through 28 February 2021, there were a total of 42,086 case reports(25,379 medically confirmed and 16,707 non-medically confirmed) containing 158,893
events. Cases were received from 63 countries.
Consistent with what was seen in Phase 2/3 of Study C4591001, most reported AEs were in
SOCs with reactogenicity events: general disorders and administration site conditions(51,335), nervous system disorders (25,957), musculoskeletal and connective tissue disorders(17,283), and gastrointestinal disorders (14,096). Post-authorization data have also informed
the addition of ADRs related to the experience of reactogenicity to the product labeling (seeSection 2.7.4.2.4.3.5 for additional information regarding ADRs).
Aside from addition of anaphylaxis and hypersensitivity, the analyses of cumulative postauthorization safety data, including a review of AESIs, are consistent with the analysis of thispivotal clinical trial. Review of post-authorization data has not revealed any novel safetyconcerns, except for anaphylaxis, and has confirmed the favorable benefit-risk profile of thevaccine.
Further details regarding the cumulative analysis of post-authorization safety data arepresented in Module 5.3.6.
2.7.4.5. Overall Conclusions
Phase 1 data from Study BNT162-01 and Study C4591001 showed that BNT162b1 and
BNT162b2 were well tolerated and both vaccines had a satisfactory reactogenicity profile inboth younger and older adults. However, BNT162b2 has a more favorable reactogenicity
profile than BNT162b1. Additionally, BNT162b2 showed less frequent systemic events inthe older compared to the younger population. BNT162b2 at 30 µg was selected for further
development in the Phase 2/3 part of the study.
In Phase 2/3, data analyzed in Study C4591001 were from blinded placebo-controlled andopen-label follow-up periods, comprised of approximately 44,000 participants ≥16 years ofage. The results were concordant with what was seen in Phase 1 and continue to show that
BNT162b2 at 30 µg, administered as 2-dose schedule (21 days apart), has an acceptable
tolerability and safety profile in individuals ≥16 years of age.
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From December 2020 until April 2021, >100 million doses of BNT162b2 have been
administered to individuals ≥16 years of age in the US under EUA.3,4 It is reassuring that themost commonly reported AEs in the post-authorization review (which includes global safety
reporting) reflect the same profile observed in the blinded placebo-controlled follow-up
period of the pivotal clinical study, primarily reflecting short-lived and resolving
reactogenicity events. Further, the same pattern was observed for pivotal study participantsoriginally randomized to the placebo group who were unblinded (per protocol) to receive
BNT162b2: these participants, in the open-label setting, also reported mostly reactogenicity
events similar to those in the blinded follow-up. AEs of clinical interest were not reported
frequently in the controlled clinical study and continue to be evaluated in the postauthorization setting.

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Overall, the risk-benefit of BNT162b2 30 µg remains favorable.

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2.7.4.6. APPENDICES
2.7.4.6.1. Appendix A: Study BNT162-01 Safety Evaluation Plan
The BNT162-01 protocol is included in Module 5.3.5.1 BNT162-01 Protocol.
2.7.4.6.1.1. Study BNT162-01 Part A Study Schema
Dose cohort schema for BNT162b1 and BNT162b2 (P/B)c

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Cohorts with younger adults

Cohorts with older adults

a)
b)
c)
d)

The data assessed by the SRC for progressing comprises 48 h data for 6 subjects.
If these cohorts use doses lower than already tested, 12 subjects may be dosed on one day in these cohorts and the cohorts may be
conducted in parallel to each other / to any dose escalation cohorts. If they use doses higher than already tested, subjects will be dosedusing a sentinel dosing/subject (2-4-6) staggering process.
For the dose regimens, see Section 2.7.4.1.1.1.2
Administration of the planned 10 µg dose in Cohort 8 requires that at least a 10 µg dose has shown acceptable tolerability in younger
adults.

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e

f

g
h

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i
j
k
l

m
n

o

p

Dipstick urine analysis: glucose, bilirubin, ketone, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocytes. Microscopic urinalysis: if warranted by dipstick results, urine sediment
was microscopically examined for the presence of red blood cells, white blood cells, casts, crystals, epithelial cells, and bacteria.
Clinical laboratory tests: (Chemistry) alkaline phosphatase, creatinine, ferritin, C-reactive protein, albumin, alanine aminotransferase, amylase, aspartate aminotransferase, gamma glutamyltranspeptidase, total bilirubin, blood urea nitrogen, glucose, lipase, sodium, potassium, calcium; (Hematology) hemoglobin, hematocrit, red blood cell count, white blood cell count and differential(neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count. Only in women who are not WOCBP: follicle stimulating hormone (FSH) at Visit 0.
Viral screening for Human Immunodeficiency Virus (HIV) 1 or 2, Hepatitis B, Hepatitis C.
Flexibility for visit days: Visit 3 Day 8±1 d; Visit 4 Day 22±2 d; Visit 5 Day 29±3 d; Visit 6 Day 43±4 d; Visit 7 Day 50±4 d; Visit 8 Day 85±7 d; Visit 9 Day 184±9d.
Only for the first 6 participants per dose group. Questioning on and documentation of AEs as well as systemic and local reactions, the latter in case of upcoming dose decision meetings.
Only IMP-related AEs.
Blood draw for anti-SARS-CoV-2 antibodies (samples will be stored until a test is commercially available).
For dose groups 1 and 8, dosing with at least 1 h intervals between participants for the first 6 participants and then with of at least 30 min intervals for the remaining 6 participants. For all other dosegroups, dosing with at least 30 min intervals between participants.
Oral swipe for SARS-CoV-2 testing either on Day -1 or at the Visit 1 on Day 1.
The listed blood draw days may be adapted if justified by the collected data. Leftover blood after completion of the immunogenicity assessments may be used for additional analyses as described inProtocol Section 8.7 (Genetics) and/or Protocol Section 8.8 (Biomarkers).
For participants who have given consent, one aliquot of the blood sample drawn for analysis of CMI may be used for HLA typing to allow additional analysis of T-cell receptor repertoire and / orphenotypic characterization of T-cells specific to vaccine-encoded antigens.
If HLA typing using the blood sample collected with Lithium Heparin is not conclusive, EDTA-blood was drawn for HLA testing.

Abbreviations: AE = adverse event; CMI = cell-mediated immune testing; D or d = day; ECG = electrocardiogram; EDTA = ethylenediamine tetraacetic acid; EoS = end of study (Visit); FU = follow-up(visit); h = hour(s); HLA = human leukocyte antigen; Day 0 = 1 d before Day 1; IMP = investigational medicinal product; min = minute(s); SARS-CoV-2 = the virus leading to COVID-19; WOCBP =women of childbearing potential.

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2.7.4.6.1.3. Study BNT162-01: Safety Assessments
2.7.4.6.1.3.1. Physical Examinations, Vital Signs, and Electrocardiograms (Study
BNT162-01)
Complete physical examinations were performed at screening. Brief physical examinations
were performed at later time points including prior boost immunizations.


A complete physical examination included, at a minimum, assessments of the
cardiovascular, respiratory, gastrointestinal and neurological systems. Height (in cm)
was also recorded during complete physical examinations.

A brief (symptom directed) physical examination included an overall healthjudgement. In-depth physical examinations were required if obvious pathologicalsigns were visible or in the case the subject states any signs or symptoms.

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Vital signs included body temperature, pulse rate, respiratory rate, and blood pressure.
Normal ranges of the vital sign parameters are presented in Module 5.3.5.1 BNT162-01
Statistical Analysis Plan Table 4. Body weight will also be recorded.
Standard 12-lead ECGs were recorded and judged by the investigator to be clinicallysignificant or not.
2.7.4.6.1.3.2. Subject Diaries (Study BNT162-01)
Subjects were given subject diaries at Visit 1 and were asked to record any reactions between
visits, solicited local reactions at the injection site (pain, tenderness, erythema/redness,
induration/swelling) and solicited systemic reactions (nausea, vomiting, diarrhea, headache,fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever [ie, ≥38°C]). Subject
diaries were collected at the visits as described in the SoA (Section 2.7.4.6.1.2).
2.7.4.6.1.3.2.1. Local Reactions (Study BNT162-01)
Assessment of local reactions after IM immunization was used to validate the solicitedassessment of local reactions in the patient diary and potentially support AE reporting.
Local reactions (both investigator assessed and solicited in the subject diaries) weree gradedusing criteria based on the guidance given in US FDA Guidance for Industry “Toxicity
Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine
Clinical Trials” for “Local Reaction to Injectable Products”. The grades are Grade 0(Absent), Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and Grade 4 (Potentially life
threatening).
The solicited local reactions were evaluated for the following time intervals:

Prime immunization up to day 7 (inclusive) after initial immunizationBoost immunization up to day 7 (inclusive) after boost immunization

Both intervals combined
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The intervals started with the date and time of the immunization.
2.7.4.6.1.3.2.2. Systemic Reactions (Study BNT162-01)
Systemic reactions after IM immunization were assessed via daily solicited reports in thesubject diaries and at the times given in the SoA (Section 2.7.4.6.1.2).
Systemic reactions were graded using criteria based on the guidance given in US FDA
Guidance for Industry “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers
Enrolled in Preventive Vaccine Clinical Trials” for “Systemic reaction grading scale”. The
grades are Grade 0 (Absent), Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe) and
Grade 4 (Potentially life threatening). Fever was graded as Mild (38.0-38.4°C), Moderate(38.5-38.9°C), Severe (39.0-40.0°C and Potentially life threatening (>40.0°C).
The solicited systemic reactions were evaluated for the following time intervals:
Prime immunization up to day 7 (inclusive) after initial immunization
Boost immunization up to day 7 (inclusive) after boost immunization

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Both intervals combined
The intervals started with the date and time of the immunization. Further details regarding
the analysis of local reactions are provided in the SAP (Module 5.3.5.1 BNT162-01
Statistical Analysis Plan Section 6.4.2).
2.7.4.6.1.3.3. Adverse Events and Serious Adverse Events (Study BNT162-01)
Adverse Events
An AE is any untoward medical occurrence in a patient or clinical study participant,temporally associated with the use of study intervention, whether or not considered related tothe study intervention.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal
laboratory finding that is clinically significant), symptom, or disease (new or exacerbated)
temporally associated with the use of study intervention.
Events after signing ICD and before study intervention administration were handled as AEs.
AEs were coded using the Updated Version MedDRA® 23.0 including specific terms for
COVID-19 to get a SOC and PT for each AE.
A TEAE is defined as any AE with an onset date on or after the first administration of study
intervention (if the AE was absent before the first administration of study intervention) or
worsened after the first administration of IMP (if the AE was present before the firstadministration of study intervention). AEs with an onset date more than 28 d after the last
administration of study intervention will be considered as treatment emergent only if
assessed as related to study intervention by the investigator.
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For more details regarding how adverse events were defined, refer to Module 5.3.5.1
BNT162-01 Protocol Section 10.3.1.1 and Section 10.3.1.2.
Suspected Adverse Reactions
A Suspected Adverse Reaction was defined as all untoward and unintended responses to a
study intervention related to any dose administered.


The definition also covers medication errors and uses outside what is foreseen in the
protocol, including misuse and abuse of the study intervention.



The definition implies a reasonable possibility of a causal relationship between theevent and the study intervention. This means that there are facts (evidence) orarguments to suggest a causal relationship.

Serious Adverse Events

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If an event was not an AE per the definition above, then it could not be an SAE even if
serious conditions were met (eg, hospitalization for signs/symptoms of the disease undertrial, death due to progression of disease).
An SAE was defined as any untoward medical occurrence that, at any dose:

Results in deathIs life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which
the trial subject was at risk of death at the time of the event. It does not refer to an
event which hypothetically might have caused death if it were more severe.



Requires trial subject hospitalization or prolongation of existing hospitalization−

In general, hospitalization signifies that the trial subject has been detained(usually involving at least an overnight stay) at the hospital or emergency ward
for observation and/or treatment that would not have been appropriate in thephysician’s office or out trial subject setting. Complications that occur duringhospitalization are AEs. If a complication prolongs hospitalization or fulfills
any other serious criteria, the event is serious. When in doubt as to whether“hospitalization” occurred or was necessary, the AE should be consideredserious.

Results in persistent disability/incapacityIs a congenital anomaly or a birth defect.

AEs of Proven COVID-19 Disease of Moderate or Severe Intensity
Any case of proven COVID-19 disease occurring during the observation period was reported
as an SAE, where the intensity of the respective AE is rated as “moderate” or “severe”(according to the criteria provided in Module 5.3.5.1 BNT162-01 Protocol Section 10.3.1.7).
If none of the other SAE definitions were deemed suitable, then the SAE criterion of being a
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2.7.4.6.2.2. Schedule of Activities (Study C4591001)
2.7.4.6.2.2.1. Study C4591001 Phase 1 SoA
An unplanned potential COVID-19 illness visit and unplanned potential COVID-19
convalescent visit are required at any time between Visit 1 (Vaccination 1) and Visit 10(24-month follow-up visit) that COVID-19 is suspected.

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Administration of BNT162b2 to Those Originally Assigned to Placebo: If a participant
became eligible for receipt of BNT162b2 or another COVID-19 vaccine according torecommendations detailed separately, and available in the electronic study reference portal,
the participant was advised to contact the site to determine whether he or she could receive
BNT162b2 in a phased manner as part of the study. When contacted, the site conducted aphone visit to confirm eligibility and, if eligible and wanting to receive BNT162b2 if theparticipant originally received placebo, unblinded study intervention allocation to determine
whether the participant received BNT162b1, BNT162b2, or placebo. If he or she originallyreceived placebo and wanted to receive BNT162b2, the participant moved to the SoA in
Section 2.7.4.6.2.2.3 for his or her remaining visits. Participants who received BNT162b1 or
BNT162b2 (at any dose level) continued in the study as originally planned.
All other participants were advised to contact the site to determine whether they can receive
BNT162b2 as part of the study no later than at the approximate time participants in Phase 2/3
reach Visit 4. When contacted, the site unblinded study intervention allocation to determine
whether the participant received BNT162b1, BNT162b2, or placebo. If he or she originallyreceived placebo and wanted to receive BNT162b2, the participant moved to the SoA in
Section 2.7.4.6.2.2.3 for his or her remaining visits.

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2.7.4.6.2.2.2. Study C4591001 Phase 2/3 SoA
An unplanned potential COVID-19 illness visit and unplanned potential COVID-19
convalescent visit are required at any time between Visit 1 (Vaccination 1) and Visit 6(24-month follow-up visit) that potential COVID-19 symptoms are reported, including
MIS-C.

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Administration of BNT162b2 to Those Originally Assigned to Placebo: If a participant≥16 years of age became eligible for receipt of BNT162b2 or another COVID-19 vaccine
according to recommendations detailed separately, and available in the electronic study
reference portal, the participant was advised to contact the site to determine whether he or
she could receive BNT162b2 in a phased manner as part of the study. When contacted, thesite conducted a phone visit to confirm eligibility and, if eligible and wanting to receive
BNT162b2 if the participant originally received placebo, unblinded study intervention
allocation to determine whether the participant received BNT162b2 or placebo. If he or she
originally received placebo and wanted to receive BNT162b2, the participant moved to the
SoA in Section 2.7.4.6.2.2.3 for his or her remaining visits. Participants who received
BNT162b2 continued in the study as originally planned.
All other participants ≥16 years of age who had not been offered the opportunity to receive
BNT162b2 were given this opportunity no later than 6 months after Vaccination 2 (at thetime of the originally planned Visit 4). If they wanted to receive BNT162b2, they were
unblinded and those who did originally receive placebo moved to the SoA in
Section 2.7.4.6.2.2.3 for their remaining visits.

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2.7.4.6.2.2.3. Administration of BNT162b2 to Those Originally Assigned to Placebo

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Participants ≥16 years of age who originally received placebo and became eligible for receiptof BNT162b2 according to recommendations detailed separately, and available in theelectronic study reference portal, had the opportunity to receive BNT162b2 in a phasedmanner as part of the study. Any placebo recipient ≥16 years of age who had not alreadybeen offered the opportunity to receive BNT162b2 was given this opportunity no later than 6months after Vaccination 2.

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2.7.4.6.2.3. Study C4591001: Safety Assessments
Safety Assessments are described in Module 5.3.5.1 C4591001 Protocol Section 8.2 andAppendix 3.
2.7.4.6.2.3.1. Electronic Diary (Study C4591001)
Certain participants were required to complete a reactogenicity e-diary (see Module 5.3.5.1
C4591001 Protocol Section 8.2.2). All participants in Phase 1, and a subset of at least thefirst 6000 participants randomized in Phase 2/3, were asked to monitor and record local
reactions, systemic events, and antipyretic medication usage for 7 days following
administration of the study intervention. Any participants in Phase 3 who are HIV-positive or
12 to 15 years of age may also have been included in this subset (will be reported at a latertime). In addition, participants 16 through 17 years of age enrolled under Protocol
Amendment 9 and onwards will be included in the reactogenicity subset. All otherparticipants, including those who originally received placebo and then received BNT162b2
under protocol amendment 10 and onwards, will not complete a reactogenicity e-diary but
will have their local reactions and systemic events detected and reported as AEs inaccordance with Module 5.3.5.1 C4591001 Protocol Section 8.3.2.

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2.7.4.6.2.3.1.1. Local Reactions (Study C4591001)
During the reactogenicity e-diary reporting period, participants were asked to assess redness,swelling, and pain at the injection site (from Day 1 through Day 7 after each dose, where Day
1 is the day of each dose) and to record the symptoms in the reactogenicity e-diary. If a local
reaction persisted beyond the end of the reactogenicity e-diary period following vaccination,
the participant was requested to report that information.
Redness and swelling was measured and recorded in measuring device units (range: 1 to 21)
and then categorized during analysis as absent, mild, moderate, or severe based on thegrading scale in Table 29. Pain at the injection site was assessed by the participant as absent,
mild, moderate, or severe according the grading scale in Table 29.
If a Grade 3 local reaction was reported in the reactogenicity e-diary, a telephone contact
occurred to ascertain further details and determine whether a site visit was clinicallyindicated. Only an investigator or medically qualified person was able to classify aparticipant’s local reaction as Grade 4. If a participant experienced a confirmed Grade 4
local reaction, the investigator was to immediately notify the sponsor and, if it wasdetermined to be related to the administration of the study intervention, further vaccinations
were to be discontinued in that participant.

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Table 29. Local Reaction Grading Scale (Study C4591001)
Mild(Grade 1)

Moderate(Grade 2)

Pain at the
injection site

Does not interferewith activity

Interferes withactivity

Redness>2.0 cm to 5.0 cm(5 to 10 measuring
device units)>2.0 cm to 5.0 cm(5 to 10 measuring
device units)>5.0 cm to 10.0 cm(11 to 20 measuring
device units)>5.0 cm to 10.0 cm(11 to 20 measuring
device units)

Swelling

Severe(Grade 3)

Potentially Life
Threatening(Grade 4)
Prevents daily activity Emergency room visit
or hospitalization forsevere pain
>10 cmNecrosis or(≥21 measuringexfoliative dermatitis
device units)>10 cmNecrosis(≥21 measuring
device units)

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2.7.4.6.2.3.1.2. Systemic Events (Study C4591001)
During the reactogenicity e-diary reporting period, participants were asked to assess
vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain, and new orworsened joint pain (from Day 1 through Day 7 after each dose, where Day 1 is the day ofeach dose) and to record the symptoms in the reactogenicity e-diary. The symptoms wereassessed by the participant as absent, mild, moderate, or severe according to the grading scalein Table 30.
If a Grade 3 systemic event was reported in the reactogenicity e-diary, a telephone contact
occurred to ascertain further details and determine whether a site visit was clinicallyindicated. Only an investigator or medically qualified person is able to classify aparticipant’s systemic event as Grade 4. If a participant experienced a confirmed Grade 4
systemic event, the investigator was to immediately notify the sponsor and, if it wasdetermined to be related to the administration of the study intervention, further vaccinations
were to be discontinued in that participant.

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Table 30. Systemic Event Grading Scale (Study C4591001)

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Mild(Grade 1)

Moderate(Grade 2)

Severe(Grade 3)

Vomiting

1-2 times in
24 hours

Diarrhea

2 to 3 loose stools 4 to 5 loose stools
in 24 hours
in 24 hours

6 or more loosestools in 24 hours

Headache

Does not interfere Some interferencewith activity
with activity

Prevents daily
routine activity

Fatigue/tiredness

Does not interfere Some interferencewith activity
with activity

Prevents daily
routine activity

Chills

Does not interfere Some interferencewith activity
with activity

Prevents daily
routine activity

New orworsened
muscle pain

Does not interfere Some interferencewith activity
with activity

Prevents daily
routine activity

New orworsened
joint pain

Does not interfere Some interferencewith activity
with activity

Prevents daily
routine activity>2 times in
24 hours

Requires IV
hydration

Potentially Life
Threatening(Grade 4)
Emergency room visit or
hospitalization for
hypotensive shock
Emergency room visit or
hospitalization for severe
diarrhea
Emergency room visit or
hospitalization for severe
headache
Emergency room visit or
hospitalization for severe
fatigue
Emergency room visit or
hospitalization for severe
chillsEmergency room visit or
hospitalization for severe
new or worsened muscle
painEmergency room visit or
hospitalization for severe
new or worsened joint pain

2.7.4.6.2.3.1.3. Fever (Study C4591001)
Temperature was collected in the reactogenicity e-diary in the evening daily during thereactogenicity e-diary reporting period. It was also collected at any time during thereactogenicity e-diary data collection periods when fever was suspected. Fever was defined
as an oral temperature of ≥38.0°C (100.4°F). The highest temperature for each day was to berecorded in the reactogenicity e-diary. Temperature was to be measured and recorded to
1 decimal place and then categorized during analysis according to the scale shown in Module
5.3.5.1 C4591001 Protocol Table 3.
If a fever of ≥39.0°C (102.1°F) was reported in the reactogenicity e-diary, a telephone
contact was to occur to ascertain further details and determine whether a site visit was
clinically indicated. Only an investigator or medically qualified person is able to confirm aparticipant’s fever as >40.0°C (>104.0°F). If a participant experienced a confirmed fever>40.0°C (>104.0°F), the investigator was to immediately notify the sponsor and, if it wasdetermined to be related to the administration of the study intervention, further vaccinations
was to be discontinued in that participant.

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2.7.4.6.2.3.2. Adverse Events and Serious Adverse Events (Study C4591001)
Definition of AE
An AE is defined as any untoward medical occurrence in a patient or clinical study
participant, temporally associated with the use of study intervention, whether or notconsidered related to the study intervention.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with theuse of study intervention.
Additional details regarding events that meet the AE definition and events that do not meet
the AE definition are provided in Module 5.3.5.1 C4591001 Protocol Section 10.3.1.
Definition of SAE

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If an event is not an AE per the definition above, then it cannot be an SAE even if serious
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death
due to progression of disease). An SAE is defined as any untoward medical occurrence that,at any dose:

Results in deathIs life-threatening

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent disability/incapacity

Is a congenital anomaly/birth defect

Other situations (as described in the protocol)

Additional details regarding SAEs are presented in Module 5.3.5.1 C4591001 Protocol
Section 10.3.2.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or
the participant's legal guardian).
Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection
period”) for each participant begins from the time the participant/parent(s)/legal guardian
provides informed consent, which is obtained before the participant’s participation in the
study (ie, before undergoing any study-related procedure and/or receiving study
intervention), through and including Visit 7 for Phase 1 participants, and Visit 3 for Phase
2/3 participants. In addition, any AEs occurring up to 48 hours after each subsequent blooddraw must be recorded on the CRF.
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SAEs will be collected from the time the participant/parent(s)/legal guardian provides
informed consent to approximately 6 months after the last dose of study intervention (Visit 8
for Phase 1 participants, and Visit 4 for Phase 2/3 participants).
Additionally, for those participants who originally received placebo but went on to receive
BNT162b2 at Vaccinations 3 and 4, AEs were collected from the time the participant
provided informed consent (for receipt of Vaccinations 3 and 4) through and including
Visit 103. SAEs were collected from the time the participant provides informed consent (forreceipt of Vaccinations 3 and 4) to approximately 6 months after the second dose of
BNT162b2 (Visit 104).
AEs and SAEs reported during the open-label follow-up period will be summarized
separately for participants who were unblinded at the time of being eligible for receipt of
BNT162b2 according to recommendations detailed separately, and available in the electronic
study reference portal, or no later than at approximately Visit 4.

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were collected from the time the participant provided informed consent (for receipt of
Vaccination 3) through and including Visit 8c (1 month after the third dose).
Follow-up by the investigator continues throughout and after the active collection period anduntil the AE or SAE or its sequelae resolve or stabilize at a level acceptable to theinvestigator and Pfizer concurs with that assessment.
For additional details regarding data collection for adverse events, refer to Module 5.3.5.1
C4591001 Protocol Section 8.3 and Module 5.3.5.1 C4591001 Statistical Analysis Plan
Section 3.1.1.4.
Intensity for each AE and SAE reported during the study was assessed as mild (Grade 1),
moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4) and assessed for causality
as described in Module 5.3.5.1 Protocol Section 10.3.3.
For information regarding recording/reporting and follow-up of AEs and/or SAEs, refer toModule 5.3.5.1 Protocol Section 10.3.3 and 10.3.4.
2.7.4.6.2.3.2.1. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying
as AEs or SAEs
Potential COVID-19 illnesses and their sequelae that are consistent with the clinical endpoint
definition should not be recorded as AEs. These data will be captured as efficacy assessment
data only on the relevant pages of the CRF, as these are expected endpoints.
Potential COVID-19 illnesses and their sequelae will not be reported according to thestandard process for expedited reporting of SAEs, even though the event may meet thedefinition of an SAE. These events will be recorded on the COVID-19 illness pages in theparticipant’s CRF within 1 day.

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NOTE: However, if either of the following conditions applies, then the event must berecorded and reported as an SAE (instead of a disease-related event):
The event is, in the investigator’s opinion, of greater intensity, frequency, or duration
than expected for the individual participant.
OR
The investigator considers that there is a reasonable possibility that the event was
related to study intervention.
Potential COVID-19 illness events and their sequelae will be reviewed by a group of internal
blinded case reviewers. Any SAE that is determined by the internal case reviewers NOT tomeet endpoint criteria is reported back to the investigator site of incidence. The investigatormust report the SAE to Pfizer Safety within 24 hours of being made aware that the SAE did
not meet endpoint criteria. The investigator’s SAE awareness date is the date on which theinvestigator site of incidence receives the SAE back from the internal case reviewers.

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2.7.4.6.2.3.3. Phase 1 Stopping Rules (Study C4591001)
Stopping rules were in place for all Phase 1 participants, based on review of AE data ande-diary reactogenicity data, until the start of Phase 2/3 or 30 days after the administration of
the second dose of study intervention in Phase 1, whichever was later.
Refer to Module 5.3.5.1 C4591001 Protocol Section 8.2.3 for additional details on Phase 1
stopping rules.
2.7.4.6.2.3.4. Surveillance of Events That Could Represent Enhanced COVID-19 andPhase 2/3 Stopping Rule (Study C4591001)
As this was a sponsor open-label study during Phase 1, the sponsor conducted unblinded
reviews of the data during the course of the study, including for the purpose of safetyassessment. Any NAAT-confirmed COVID-19 cases in Phase 1 were to be reviewed
contemporaneously by the IRC and the DMC.
In Phase 2/3, the unblinded team supporting the DMC, including an unblinded medical
monitor, will review cases of severe COVID-19 as they are received and will review AEs atleast weekly for additional potential cases of severe COVID-19. At any point, the unblinded
team may discuss with the DMC chair whether the DMC should review cases for an adverse
imbalance of cases of COVID-19 and/or severe COVID-19 between the vaccine and placebogroups.
Stopping and alert rules were to be applied (see Module 5.3.5.1 C4591001 Protocol
Section 8.2.4). Participants were instructed when to contact the site due to potential COVID19 illness (see Module 5.3.5.1 C4591001 Protocol Section 8.13). Reporting and review ofpotential COVID-19 illness is further detailed in Module 5.3.5.1 C4591001 Protocol
Section 8.3.7.

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2.7.4.6.2.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure

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Details regarding exposure during pregnancy or breastfeeding and occupational exposure arepresented in Module 5.3.5.1 C4591001 Protocol Section 8.3.5.

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2.7.4.6.3. Appendix C: Phase 2 Study C4591001 Post-text Tables
2.7.4.6.3.1. Reactogenicity (Phase 2, Study C4591001, Post-text Tables and Figures)
2.7.4.6.3.1.1. Local Reactions (Phase 2, Study C4591001, Post-text Tables and Figures)

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Figure 9. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days
After Each Dose – Phase 2 – Safety Population

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Figure 10. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days
After Each Dose, Phase 2 - Age Group: 18-55 Years – Safety Population

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Figure 11. Subjects Reporting Local Reactions, by Maximum Severity, Within 7 Days
After Each Dose, Phase 2 – Age Group: 56-85 Years – Safety Population

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2.7.4.6.3.1.2. Systemic Events (Phase 2, Study C4591001, Post-text Tables and Figures)

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Figure 12. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose – Phase 2 – Safety
Population

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Figure 13. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose, Phase 2 –Age Group: 18-55 Years – Safety Population

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Figure 14. Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After Each Dose, Phase 2 –Age Group: 56-85 Years – Phase 2 – Safety Population

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2.7.4.6.4. Appendix D: Phase 3 Study C4591001 Post-text Tables
2.7.4.6.4.1. Exposure, Disposition, and Study Population Characteristics (Phase 3, Study
C4591001, Post-text Tables)

Table 31. Disposition of All Randomized Subjects – Phase 2/3 Subjects ≥16 Yearsof AgeVaccine Group (as Randomized)

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Randomized
Not vaccinatedOriginal blinded placebo-controlled follow-up period
VaccinatedDose 1
Dose 2
Discontinued from original blinded placebo-controlled
vaccination periodc
Reason for discontinuation
Lost to follow-up
Withdrawal by subject
No longer meets eligibility criteria
Adverse event
Physician decision
Pregnancy
Protocol deviation
Death
Medication error without associated adverse event
Withdrawal by parent/guardian
Other
Unblinded before 1-month post–Dose 2 visit
Completed 1-month post–Dose 2 visit
Withdrawn from the study
Withdrawn after Dose 1 and before Dose 2
Withdrawn after Dose 2 and before 1-month post–Dose 2
visit
Withdrawn after 1-month post–Dose 2 visit
Reason for withdrawal from the study
Lost to follow-up
Withdrawal by subject
Protocol deviation
Death
Adverse event
Physician decision

BNT162b2 (30 μg)(Na=22085)
nb (%)

Placebo(Na=22080)
nb (%)

Total(Na=44165)
nb (%)

22085 (100.0)
55 (0.2)22080 (100.0)
50 (0.2)

44165 (100.0)
105 (0.2)22030 (99.8)22030 (99.8)
21675 (98.1)

22030 (99.8)22030 (99.8)
21650 (98.1)

44060 (99.8)
44060 (99.8)
43325 (98.1)

352 (1.6)

528 (2.4)880 (2.0)

151 (0.7)
109 (0.5)
26 (0.1)
27 (0.1)
5 (0.0)6 (0.0)3 (0.0)3 (0.0)3 (0.0)1 (0.0)18 (0.1)

153 (0.7)
181 (0.8)120 (0.5)
26 (0.1)
8 (0.0)6 (0.0)8 (0.0)4 (0.0)2 (0.0)0
20 (0.1)

304 (0.7)290 (0.7)
146 (0.3)
53 (0.1)
13 (0.0)
12 (0.0)
11 (0.0)
7 (0.0)5 (0.0)1 (0.0)38 (0.1)

253 (1.1)
21382 (96.8)240 (1.1)
21293 (96.4)

493 (1.1)
42675 (96.6)

343 (1.6)
176 (0.8)
100 (0.5)484 (2.2)
211 (1.0)
139 (0.6)827 (1.9)387 (0.9)239 (0.5)

67 (0.3)

134 (0.6)201 (0.5)

174 (0.8)122 (0.6)
11 (0.0)
16 (0.1)
9 (0.0)3 (0.0)191 (0.9)226 (1.0)
24 (0.1)
15 (0.1)
8 (0.0)6 (0.0)365 (0.8)348 (0.8)
35 (0.1)
31 (0.1)
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Table 31. Disposition of All Randomized Subjects – Phase 2/3 Subjects ≥16 Yearsof AgeVaccine Group (as Randomized)

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No longer meets eligibility criteria
Pregnancy
Medication error without associated adverse event
Withdrawal by parent/guardian
Other
Open-label follow-up period
Originally randomized to BNT162b2
Received Dose 2/unplanned doseCompleted 1-month post–Dose 2 visit
Completed 6-month post–Dose 2 visit
Withdrawn from the study
Withdrawn before 6-month post–Dose 2 visit
Withdrawn after 6-month post–Dose 2 visit
Reason for withdrawal from the study
Withdrawal by subject
Protocol deviation
Lost to follow-up
Death
Physician decision
Adverse event
No longer meets eligibility criteria
Other

BNT162b2 (30 μg)(Na=22085)
nb (%)

Placebo(Na=22080)
nb (%)

Total(Na=44165)
nb (%)

1 (0.0)01 (0.0)1 (0.0)5 (0.0)4 (0.0)1 (0.0)009 (0.0)5 (0.0)1 (0.0)1 (0.0)1 (0.0)14 (0.0)20404 (92.4)
87 (0.4)
210 (1.0)6414 (29.0)
105 (0.5)103 (0.5)
2 (0.0)56 (0.3)
35 (0.2)
4 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)3 (0.0)

Originally randomized to placebo
Withdrawn from the study after unblinding and before
Dose 3
Received Dose 3 (first dose of BNT162b2 [30 μg])
Received Dose 4 (second dose of BNT162b2 [30 μg])20948 (94.9)
497 (2.3)

Discontinued from open-label vaccination periodd
Reason for discontinuation from open-label vaccination
periodProtocol deviation
Adverse event
Withdrawal by subject
Pregnancy
Death
Lost to follow-up

24 (0.1)

Completed 1-month post–Dose 4 visit

19612 (88.8)
15986 (72.4)

6 (0.0)5 (0.0)5 (0.0)4 (0.0)2 (0.0)2 (0.0)7209 (32.6)

Withdrawn from the study
Withdrawn after Dose 3 and before Dose 4

14 (0.1)
11 (0.0)

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Table 31. Disposition of All Randomized Subjects – Phase 2/3 Subjects ≥16 Yearsof AgeVaccine Group (as Randomized)
BNT162b2 (30 μg)(Na=22085)
nb (%)

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Withdrawn after Dose 4 and before 1-month post–Dose 4
visit
Withdrawn after 1-month post–Dose 4 visit
Reason for withdrawal from the study
Withdrawal by subject
Protocol deviation
Death
Adverse event
Lost to follow-up

Placebo(Na=22080)
nb (%)

Total(Na=44165)
nb (%)

2 (0.0)1 (0.0)7 (0.0)3 (0.0)2 (0.0)1 (0.0)1 (0.0)Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversightare not included in any analysis population.
Note: Because of a dosing error, Subjects C4591001 1081 10811053, C4591001 1088 10881077, C4591001 1177
11771089 and C4591001 1231 12311057 received an additional dose of BNT162b2 (30 µg) at an unscheduled visit after
receiving 1 dose of BNT162b2 (30 µg) and 1 dose of placebo.
a. N = number of randomized subjects in the specified group, or the total sample. This value is the denominator for thepercentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Original blinded placebo-controlled vaccination period is defined as the time period from Dose 1 to 1 month post–
Dose 2.
d. Open-label vaccination period is defined as the time period from Dose 3 (first dose of BNT162b2 [30 µg]) to 1 monthpost–Dose 4 (second dose of BNT162b2 [30 µg]).
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (19:20) Source Data: adds Table Generation: 27MAR2021(16:34)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adds s002 all p3 rand

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Table 32. Vaccine as Administered by Vaccine Group – Phase 2/3 Subjects ≥16
Years of Age – All Randomized Subjects
Vaccine Group (as Randomized)

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Vaccine (as Administered)

BNT162b2 (30 μg)(Na=22085)
nb (%)

Placebo(Na=22080)
nb (%)

22030 (99.8)
55 (0.2)22030 (99.8)
50 (0.2)

22026 (99.7)
2 (0.0)2 (0.0)4 (0.0)22025 (99.8)
1 (0.0)21756 (98.5)
3 (0.0)05 (0.0)21645 (98.0)
0

VaccinatedNot vaccinatedDose 1
BNT162b2 (30 μg)
PlaceboIndeterminate vaccinec
Dose 2
BNT162b2 (30 μg)
PlaceboIndeterminate vaccinec
Dose 3First dose BNT162b2 (30 μg)
Indeterminate vaccinec
Dose 4
Second dose BNT162b2 (30 μg)
Indeterminate vaccinec

19612 (88.8)
015986 (72.4)0Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. "Indeterminate vaccine" refers to subjects whose vaccine (as administered) could not be determined.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(01:28)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/advx_s002_adm_p3_rand

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Table 33. Vaccine Administration Timing – Phase 2/3 Subjects ≥16 Years of Age –All Randomized Subjects

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Vaccine Group (as Randomized)
BNT162b2 (30 μg)(Na=22085)
nb (%)

Placebo(Na=22080)
nb (%)

Randomized
Not vaccinated22085 (100.0)
55 (0.2)22080 (100.0)
50 (0.2)

Dose 122030 (99.8)22030 (99.8)

Dose 2c21759 (98.5)07374 (33.4)
13823 (62.6)
249 (1.1)
96 (0.4)
59 (0.3)
43 (0.2)
115 (0.5)21650 (98.1)
2 (0.0)7283 (33.0)13850 (62.7)
300 (1.4)
90 (0.4)
47 (0.2)
38 (0.2)
40 (0.2)<14 Days
14 to 20 Days
21 to 27 Days
28 to 34 Days
35 to 41 Days
42 to 48 Days
49 to 55 Days
>55 Days
Dose 3 (first dose of BNT162b2 [30 μg])

19612 (88.8)

Dose 4 (second dose of BNT162b2 [30 μg])d

15986 (72.4)
2 (0.0)4980 (22.6)
10617 (48.1)
247 (1.1)
92 (0.4)
34 (0.2)
12 (0.1)
2 (0.0)<14 Days
14 to 20 Days
21 to 27 Days
28 to 34 Days
35 to 41 Days
42 to 48 Days
49 to 55 Days
>55 Days

Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Days calculated since Dose 1.
d. Days calculated since Dose 3.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(01:37)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/advx s002 time p3 rand

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Table 34. Safety Population – Phase 2/3 Subjects ≥16 Years of Age
Vaccine Group (as Administered)Randomizedb
Vaccinated090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Safety population
HIV-positive
Indeterminate vaccinec
Excluded from safety population
Reason for exclusion
Subject did not receive study vaccine
Unreliable data due to lack of PI oversight

BNT162b2 (30 μg)
naPlacebona

Total
na (%)

22032

22025

44165
44060 (99.8)

22026
100

22021
100

44050 (99.7)
200 (0.5)
3 (0.0)115 (0.3)
105 (0.2)
10 (0.0)

Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. n = Number of subjects with the specified characteristic, or the total sample.
b. This value is the denominator for the percentage calculations.
c. "Indeterminate vaccine" refers to subjects whose vaccine group (as administered) could not be determined. These
subjects were not included in the safety analysis but their safety data is listed separately.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(01:42)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adsl s003 pop all p3

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Table 35. Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age –Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=22026)
nb (%)

Placebo(Na=22021)
nb (%)

Total(Na=44047)
nb (%)

Subjects (%) with length of follow-up of:
Original blinded placebo-controlled follow-up period<2 Months

1251 (5.7)

1331 (6.0)

2582 (5.9)≥2 Months to <4 months

7744 (35.2)

8070 (36.6)

15814 (35.9)≥4 Months to <6 months

11253 (51.1)

11316 (51.4)

22569 (51.2)≥6 Months

1778 (8.1)

1304 (5.9)

3082 (7.0)

Total exposure from Dose 2 to cutoff date

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)<2 Months

390 (1.8)≥2 Months to <4 months

679 (3.1)≥4 Months to <6 months

8951 (40.6)≥6 Months

12006 (54.5)

Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage
calculations.
b. n = Number of subjects with the specified characteristic.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(01:37)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adsl_fu_d2_p3_saf

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Table 36. Demographic Characteristics – Subjects With at Least 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

BNT162b2 (30 μg)(Na=12006)
nb (%)
Sex
Male
Female6040 (50.3)
5966 (49.7)

Race
White
Black or African American
American Indian or Alaska Native
Asian
Native Hawaiian or other Pacific IslanderMultiracial
Not reported

10370 (86.4)
851 (7.1)
55 (0.5)452 (3.8)
31 (0.3)
195 (1.6)
52 (0.4)

Racial designation
Japanese

44 (0.4)

Ethnicity
Hispanic/Latino
Non-Hispanic/non-Latino
Not reported

3339 (27.8)8604 (71.7)
63 (0.5)

Country
Argentina
BrazilUSA

2118 (17.6)
596 (5.0)9292 (77.4)

Age group (at vaccination)
16-55 Years>55 Years

6666 (55.5)
5340 (44.5)

Age at vaccination (years)
Mean (SD)MedianMin, max

51.4 (15.44)
53.0(18, 85)

Baseline SARS-CoV-2 status
Positivec
Negatived
Missing

250 (2.1)
11678 (97.3)
78 (0.6)

Body mass index (BMI)
Underweight (<18.5 kg/m2)
Normal weight (≥18.5 kg/m2 - 24.9 kg/m2)
Overweight (≥25.0 kg/m2 - 29.9 kg/m2)

136 (1.1)
3527 (29.4)
4232 (35.2)

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Table 36. Demographic Characteristics – Subjects With at Least 6 Months of
Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age(Subjects Who Originally Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=12006)
nb (%)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Obese (≥30.0 kg/m2)
Missing

4107 (34.2)
4 (0.0)Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Positive N-binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID-19.
d. Negative N-binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID-19.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(15:19)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2_unblinded/C4591001_BLA/adsl_s005_demo_6m_p3_saf

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Table 37. Demographic Characteristics – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After Unblinding – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

BNT162b2 (30 μg)(Na=19611)
nb (%)
Sex
Male
Female9841 (50.2)
9770 (49.8)

Race
White
Black or African American
American Indian or Alaska Native
Asian
Native Hawaiian or other Pacific IslanderMultiracial
Not reported

16299 (83.1)
1636 (8.3)
189 (1.0)
849 (4.3)
28 (0.1)
509 (2.6)
101 (0.5)

Racial designation
Japanese

77 (0.4)

Ethnicity
Hispanic/Latino
Non-Hispanic/non-Latino
Not reported

5002 (25.5)
14499 (73.9)
110 (0.6)

Country
Argentina
BrazilGermanySouth Africa
TurkeyUSA2612 (13.3)
1428 (7.3)
241 (1.2)
362 (1.8)
242 (1.2)
14726 (75.1)

Age group (at vaccination)
16-55 Years>55 Years

11404 (58.2)
8207 (41.8)

Age at vaccination (years)
Mean (SD)MedianMin, max

50.1 (15.91)
51.0(16, 91)

Baseline SARS-CoV-2 status
Positivec
Negatived
Missing

590 (3.0)
18909 (96.4)
112 (0.6)

Body mass index (BMI)

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Table 37. Demographic Characteristics – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After Unblinding – Phase 2/3
Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)(Na=19611)
nb (%)

090177e196f5180a\Approved\Approved On: 05-May-2021 14:36 (GMT)

Underweight (<18.5 kg/m2)
Normal weight (≥18.5 kg/m2 - 24.9 kg/m2)
Overweight (≥25.0 kg/m2 - 29.9 kg/m2)
Obese (≥30.0 kg/m2)
Missing

258 (1.3)5805 (29.6)
6790 (34.6)
6753 (34.4)
5 (0.0)Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
Note: Human immunodeficiency virus (HIV)-positive subjects are included in this summary but analyzed and reported
separately.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Positive N-binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID-19.
d. Negative N-binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID-19.
PFIZER CONFIDENTIAL SDTM Creation: 25MAR2021 (23:24) Source Data: adsl Table Generation: 27MAR2021(15:20)(Cutoff Date: 13MAR2021, Snapshot Date: 25MAR2021) Output File:./nda2 unblinded/C4591001 BLA/adsl s005 demo cr p3 saf

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2.7.4.7. REFERENCES
1

US Food and Drug Administration, Guidance for Industry Toxicity Grading Scale for
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial.
Rockville, MD: Center for Biologics Evaluation and Research; September 2007.
Available: Available at: https://www.fda.gov/media/73679/download. Accessed:
30 November 2020.

2

Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med
1985;4(2):213-26.

3Centers for Disease Control and Prevention (CDC). COVID-19 Data Tracker. Available
at: https://covid.cdc.gov/covid-data-tracker/#vaccinations. Accessed 23 April 2021.

4Coronavirus (COVID-19) Vaccinations – Statistics and Research – Our World in Data.
Available at: https://ourworldindata.org/covid-vaccinations#which-vaccines-have-beenadministered-in-each-country. Accessed 23 April 2021.

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