Breakthroughs that change patients’ lives Confidential

1

COVID-19 Vaccine

BNT162b2 

Safety, Immunogenicity, and 

Efficacy in Subjects 12–15

-

years-old

Presentation to ACIP

12 May 2021

John L. Perez, MD, MBA, MA
Worldwide Research, Development and Medical Confidential 2

Inclusion of adolescents <16 yrs of age

• C4591001 was initially an adult study

• Once acceptable tolerance in adults was established within the original study the protocol was 

amended to allow inclusion of subjects 16-17 years of age and subsequently 12-15 years of age at 

the same dose and schedule as adults, without further dose-finding. 

• The purpose was to generate data to understand whether people 12-15 years of age could be 

included in pandemic COVID-19 immunisation programmes

• Data is from dose 1 to 1 month post dose 2 (12-15- and 16–25-year-olds); and from dose 1 to data 

cut-off point (13 March 2021) – 12–15-year-olds

• Data from subjects 16-25 years of age were used for the safety comparisons and immunobridging

purposes 
Worldwide Research, Development and Medical Confidential 3

Phase 2/3 Safety Schema – Started 27 July, 2020

Up to

2 years

21 days

apart

Active surveillance

for potential COVID-19 symptoms TRIGGERING 

telehealth or in-person visit and nasal swab

7 days 7 days

Reactogenicity in subsets for 16 and above; all 12-15 year olds

Non-serious AE: all participants

One month post dose 2

Serious AE: all participants

Six months post dose 2

Deaths: all participants

Vaccination period Follow-up period

Through study

• All 12-15 year olds had e-diaries to capture solicited events (N=2260)

• A random subset of 16-25 year olds had e-diaries (N=1097)

• Prior history of symptomatic COVID-19/MIS-C were excluded
Worldwide Research, Development and Medical Confidential 4

Demography for 12-15 and 16-25 year olds (Safety population)

BNT162b2 Placebo

12-15 Years

(N=1131) n (%)

16-25 Years

(N=1867) n (%)

12-15 Years

(N=1129) n (%)

16-25 Years

(N=1903) n (%)

Sex

Male 567 (50.1) 921 (49.3) 585 (51.8) 882 (46.3)

Female 564 (49.9) 946 (50.7) 544 (48.2) 1021 (53.7)

Race

White 971 (85.9) 1443 (77.3) 962 (85.2) 1510 (79.3)

Black or African American 52 (4.6) 189 (10.1) 57 (5.0) 179 (9.4)

American Indian or Alaska native 4 (0.4) 32 (1.7) 3 (0.3) 18 (0.9)

Asian 72 (6.4) 108 (5.8) 71 (6.3) 108 (5.7)

Native Hawaiian or other Pacific 

Islander 3 (0.3) 10 (0.5) 0 3 (0.2)

Multiracial 23 (2.0) 76 (4.1) 29 (2.6) 74 (3.9)

Not reported 6 (0.5) 9 (0.5) 7 (0.6) 11 (0.6)

Racial desig. Japanese 5 (0.4) 3 (0.2) 2 (0.2 6 (0.3)

Ethnicity

Hispanic/Latino 132 (11.7) 604 (32.4) 130 (11.5) 575 (30.2)

Non-Hispanic/non-Latino 997 (88.2) 1259 (67.4) 996 (88.2) 1322 (69.5)

Not reported 2 (0.2) 4 (0.2) 3 (0.3) 6 (0.3)

Country

USA 1131 (100.0) 1333 (71.4) 1129 (100.0) 1364 (71.7)

Others* 0 534 (28.6) 0 539 (28.3)

*Argentina, Brazil, Germany, South Africa, Turkey Note: All 12-15 year olds from the US; ~72% of 16-25 year olds from the US
Reactogenicity in 12-15 year olds and 16-25 year olds
Worldwide Research, Development and Medical Confidential 6

Subjects Reporting Local Reactions, by Maximum Severity, Within 7 

Days After Each Dose in 12-15 and 16-25 Year Olds

Mild Moderate Severe Grade 4

Redness Swelling Pain at Injection Site

5.8% 1.1% 6.4% 0.9% 6.9% 1.0%

8.3%

1.1%

86.2%

23.3%

83.4%

15.9%

0%

20%

40%

60%

80%

100%

30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo

12-15 16-25 12-15 16-25 12-15 16-25

5.0% 0.9% 5.7% 0.2% 4.9% 0.6% 6.8% 0.2%

78.9%

17.9%

77.5%

12.1%

0%

20%

40%

60%

80%

100%

30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo 30 μg Placebo

12-15 16-25 12-15 16-25 12-15 16-25

Dose 1 Dose 2

Redness and sweeling severity definition: Mild= >2-5cm, Moderate= >5-10 cm; Severe= >10 cm; Grade 4= necrosis

Pain at injection site severity definition: Mild=no interference; Moderate=some interference; Severe=prevents daily activity; Grade 4=ER visit or hospitalization 

Dose 1: 12-15 yrs N=2254; 16-25 yrs N=1084 Dose 2: 12-15 yrs N=2175 16-25 yrs N=984
Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After 

Dose 1 in 12-15 and 16-25 Year Olds

Systemic events: Mild Moderate Severe Grade 4

Fever: 38.0 °C-38.4 °C 38.4 °C-38.9 °C 38.9 °C-40.0 °C >40.0 °C

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle

Pain

Joint

Pain

10.1% 7.3%

60.1% 59.9% 55.3% 53.9%

27.6% 25.0%

2.8% 1.7% 8.0% 10.7%

24.1% 26.9%

9.7% 13.2%

0%

20%

40%

60%

80%

100%

12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25

1.1% 1.4%

40.6% 38.5% 35.1% 37.1%

9.7% 8.5%

0.9% 1.6% 7.3% 11.2% 13.1% 14.1%

6.8% 5.1%

0%

20%

40%

60%

80%

100%

12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25

BNT162b2 Placebo

Worldwide Research, Development and Medical Confidential 7

Fatigue, headache, chills, muscle pain, joint pain severity definition: Mild=no interference; Moderate=some interference; Severe=prevents daily activity; Grade 4=ER visit or hospitalization

Vomiting severity definition: Mild=1-2 time in 24h; Moderate=>2times in 24h; Severe=Requires IV hydration; Grade 4=ER visit or hospitalization

Diarrhea severity definition: Mild=2-3 times in 24h; Moderate=4-5 times in 24h; Severe=6 or more times in 24h; Grade 4=ER visit or hospitalization 

Dose 1: 12-15 yrs N=2254; 16-25 yrs N=1084 
Subjects Reporting Systemic Events, by Maximum Severity, Within 7 Days After 

Dose 2 in 12-15 and 16-25 Year Olds

Systemic events: Mild Moderate Severe Grade 4

Fever: 38.0 °C-38.4 °C 38.4 °C-38.9 °C 38.9 °C-40.0 °C >40.0 °C

Fever Fatigue Headache Chills Vomiting Diarrhea Muscle

Pain

Joint

Pain

19.6% 17.2%

66.2% 65.6% 64.5% 60.9%

41.5% 40.0%

2.6% 2.7% 5.9% 8.0%

32.4%

40.8%

15.8% 21.9%

0%

20%

40%

60%

80%

100%

12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25

0.6% 0.4%

24.5% 23.2% 24.4% 23.8%

6.8% 4.4% 1.1% 1.8% 4.0% 5.2% 8.3% 9.7% 4.7% 4.0%

0%

20%

40%

60%

80%

100%

12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25 12-15 16-25

BNT162b2 Placebo

Worldwide Research, Development and Medical Confidential 8

Fatigue, headache, chills, muscle pain, joint pain severity definition: Mild=no interference; Moderate=some interference; Severe=prevents daily activity

Vomiting severity definition: Mild=1-2 time in 24h; Moderate=>2times in 24h; Severe=Requires IV hydration; Grade 4=ER visit or hospitalization

Diarrhea severity definition: Mild=2-3 times in 24h; Moderate=4-5 times in 24h; Severe=6 or more times in 24h; Grade 4=ER visit or hospitalization 

Dose 2: 12-15 yrs N=2175 16-25 yrs N=984

; Grade 4=ER visit or hospitalization
Worldwide Research, Development and Medical Confidential 9

• Local reactions were predominantly pain at the injection site – more prominent 

after the first dose

• Mostly mild to moderate

• Systemic events were predominantly fatigue, headaches, chills and muscle pain 

as well as fever and joint pain – more prominent after the second dose

• Mostly mild to moderate

Conclusions: Local reactions and systemic events Phase 3 within 7 

days of each dose – 12-15 yr olds (N=2254)
Adverse events in Phase 3 – 12-15 year olds and 16-25 

year olds
Worldwide Research, Development and Medical Confidential 11

Overall Adverse Events from Dose 1 to 1 Month Post Dose 2

12-15 (N=2260) and 16-25 (Reactogenicity subset N=1097) year olds

Any AE Related AE Any SAE Related SAE Withdrawal due to AE Death

0

20

40

60

80

100

8.0 2.1 0.4 0 0.4 0

10.8 6.2 Proportion of subjects (%) 0.4 0 0.2 0 Reporting at least 1 AE

BNT162b2 Placebo

16-25 Year olds

Any AE Related AE Any SAE Related SAE Withdrawal due to AE Death

0

20

40

60

80

100

5.9 1.9 0.1 0 0 0

6.0 Proportion of subjects (%) 2.9 0.4 0 0.2 0 Reporting at least 1 AE

BNT162b2 Placebo

12-15 Year olds
Worldwide Research, Development and Medical Confidential 12

Overall Adverse Events from Dose 1 to Data Cut-off Date (13Mar2021)

12-15 year olds (N=2260)

Any AE Related AE Any SAE Related SAE Withdrawal due to AE Death

0

20

40

60

80

100

6.3 1.9 0.2 0 0 0

6.4 Proportion of subjects (%) 2.9 0.4 0 0.2 0 Reporting at least 1 AE

BNT162b2 Placebo
Worldwide Research, Development and Medical Confidential 13

Adverse Events ≥1.0% by System Organ Class for 12-15 year olds 

1 Month Post Dose 2

 

6.0

1.4

1.2

1.1

0.5

5.9

1.0

0.3

0.6

1.2

0 20 40 60 80 100

BNT162b2 (N=1131) Placebo (N=1129)

General disorders and 

dministration site conditions1

Gastrointestinal disorders2

Nervous system disorders3

Skin and subcutaneous 

tissue disorders

Any event

a

Percent of Subjects Reporting ≥1% AE

1. Predominantly reflect local reactions at the injection site and systemic reactions of fever and fatigue 

2. Predominantly reflect nausea and diarrhea

3. Predominantly reflects Headache
Adverse Events ≥1.0% by System Organ Class for 16-25 year olds 

1 Month Post Dose 2

10.8

3.9

2.4

2.2

0.9

0.9

0.6

8.0

1.8

1.2

1.4

1.1

2.1

1.1

0 20 40 60 80 100

BNT162b2 (N=536) Placebo (N=561)

General disorders and 

administration site conditions1

Nervous system disorders2

Musculoskeletal and connective 

tissue disorders3

Injury, poisoning and procedural 

complications

Any event

Gastrointestinal disorders4

Infections and infestations

Worldwide Research, Development and Medical Confidential 14

Percent of Subjects Reporting ≥1 AE

1. Predominantly reflect local reactions at the injection site and systemic reactions of fatigue and chills 

2. Predominantly reflects Headache 

3.. Predominantly reflect myalgias and arthralgia’s as part of systemic events

4. Predominantly reflects Nausea and Vomiting
Adverse Events ≥1.0% by System Organ Class for 12-15 year olds 

from Dose 1 to Data Cut-off Date (13 Mar 2021)

6.4

1.4

1.2

1.1

0.8

0.6

6.3

1.0

0.3

0.6

1.2

1.2

0 20 40 60 80 100

BNT162b2 (N=1131) Placebo (N=1129)

General disorders and 

administration site conditions1

Gastrointestinal disorders2

Nervous system disorders3

Skin and subcutaneous 

tissue disorders

Any event

Percent of Subjects Reporting ≥1 AE

Injury, poisoning and procedural 

complications

Worldwide Research, Development and Medical Confidential 15

1. Predominantly reflect local reactions at the injection site and systemic reactions of fever and fatigue 

2. Predominantly reflect nausea and diarrhea

3. Predominantly reflects Headache
Worldwide Research, Development and Medical Confidential 16

• 9 cases (0.8%) in BNT162b2 and 2 cases placebo (0.2%)

• 7 (0.6%) were related to vaccination; 1 (0.1%) in the placebo group 

• Primarily Left axillary or Left cervical 

• Onset within 2-10 days after vaccination

• Duration 1-10 days where reported (others were ongoing at the time of the data cutoff date).

• In adults (16-55 years of age), 52 participants (0.4%) in the BNT162b2 group and 2 participants 

(0.0%) in the placebo group had lymphadenopathy events reported up to the unblinding date and 

assessed by the investigator as related to study intervention.

• The majority of these events occurred in the arm and neck region, were reported within 2-4 days after 

vaccination (usually after Dose 2), and typically resolved within approximately 1 week.

Lymphadenopathy in 12-15 Year Olds
Worldwide Research, Development and Medical Confidential 17

Serious Adverse Events by SOC/PT from Dose 1 to Data Cut-off Date

12-15 year olds

System Organ Class/PT

BNT162b2 (30 μg)

(N=1131)

Placebo

(N=1129)

n % n %

ANY EVENT 5 0.4 2 0.1

GASTROINTESTINAL DISORDERS

*Abdominal pain

*Constipation

1

1

1

0.1

0.1

0.1

0

0

0

0

0

0

INFECTIONS AND INFESTATIONS

#Appendicitis

#Focal peritonitis

0

0

0

0

0

0

2

2

1

0.2

0.2

0.1

NERVOUS SYSTEM DISORDERS

*Neuralgia

1

1

0.1

0.1

0

0

0

0

PSYCHIATRIC DISORDERS

Depression

Anxiety

Suicidal ideation

4

3

1

1

0.4

0.3

0.1

0.1

0

0

0

0

0

0

0

0

*Abdominal pain, constipation and neuralgia were in the same participant

#Appendicitis and focal peritonitis were in the same participant
Worldwide Research, Development and Medical Confidential 18

Deaths: 12–15-year-olds

• No deaths
Efficacy and Immunogenicity
Worldwide Research, Development and Medical Confidential 20

Follow-up Time After Dose 2: 12-15 year olds – Safety Population

Total exposure from 

Dose 2 to cut-off date

BNT162b2 (30 μg)

(N=1131)

n

b

(%)

Placebo

(N=1129)

n (%)

Total

(N=2260)

n (%)

< 1 Month 13 (1.1) 25 (2.2) 38 (1.7)

≥1 Month to < 2 months 458 (40.5) 456 (40.4) 914 (40.4)

≥2 Months to <3 months 612 (54.1) 599 (53.1) 1211 (53.6)

≥3 Months 48 (4.2) 49 (4.3) 97 (4.3)

Note: 98.3% of subjects had at least 1 month of follow-up time
Worldwide Research, Development and Medical Confidential 21

Geometric Mean Titers: SARS-CoV-2 Neutralization Assay – NT50* – Subjects 12-15 and 

16-25 Years of Age (Immunogenicity Subset) – Dose 2 Evaluable Immunogenicity 

Population (All subjects)

Day 1 Day 52

(1M PD2) Day 1 Day 52(1M PD2) Day 1 Day 52(1M PD2) Day 1 Day 52(1M PD2)

1

10

100

1000

10000

10.0 10.5 10.7

730.8

11.2 15.1 11.2

1283.0 NT50 (titer) GMT

BNT2 Placebo BNT2 Placebo

12-15 Year olds 16-25 Year olds *NT50 = 50% neutralizing titers
Worldwide Research, Development and Medical Confidential 22

Noninferiority Between 12-15 and 16-25 years Of Age Was Met

Geometric Mean Ratio (GMR) in Neutralization Titers

(Without prior infection)

BNT162b2 (30 μg)

12-15 year 16-25 years 12-15/16-25 years

Assay

Dosing/

Sampling 

Time Point n

GMT 

(95% CI) n

GMT 

(95% CI)

GMR

(95% CI)

Met NI 

(Y/N)

SARS-CoV-2 

neutralization assay -

NT50 (titer)

2 / 1 Month 190 1239.5

(1095.5, 1402.5) 170 705.1(621.4, 800.2)

1.76

(1.47, 2.10) Y

• Noninferiority is declared if the lower bound of the 95% confidence interval is > 0.67

• LBCI for GMR >1 indicating a statistically greater response in 12-15 that 16-25 year olds
Worldwide Research, Development and Medical Confidential 23

First COVID-19 Occurrence From 7 Days After Dose 2 

Subjects 12-15 Years of Age – Evaluable Efficacy Population

BNT162b2 (30 μg)

N=1005

Placebo

N=978

Efficacy Endpoint n

Surveillance 

Time (n) n

Surveillance 

Time (n) VE (%) (95% CI)

First COVID-19 occurrence ≥7 

days after Dose 2 0 0.154 (1001) 16 0.147 (972) 100.0 (75.3, 100.0)

Subjects WITHOUT Evidence of Infection Prior to 7 days after Dose 2

Total surveillance time: 1000 person-years for all subjects within each group at risk for the endpoint.

The analysis is descriptive; no hypothesis test

• There were no severe COVID-19 cases
Worldwide Research, Development and Medical Confidential 24

First COVID-19 Occurrence From 7 Days After Dose 2 

Subjects 12-15 Years of Age – Evaluable Efficacy Population

BNT162b2 (30 μg)

N=1119

Placebo

N=1110

Efficacy Endpoint n

Surveillance 

Time (n) n

Surveillance 

Time (n) VE (%) (95% CI)

First COVID-19 occurrence ≥7 

days after Dose 2 0 0.170 (1109) 18 0.163 (1094) 100.0 (78.1, 100.0)

Subjects WITH or WITHOUT Evidence of Infection Prior to 7 days after Dose 2

Total surveillance time: 1000 person-years for all subjects within each group at risk for the endpoint.

The analysis is descriptive; no hypothesis test

• There were no severe COVID-19 cases
Worldwide Research, Development and Medical Confidential 25

• Reactogenicity: BNT162b2 was well tolerated in subjects 12-15 years old and showed a 

similar pattern to that seen in 16-25 year olds 

• Pain at the injection site, fatigue, headaches, chills, joint pain and muscle pain were the most 

predominant as well as fever

• Increased systemic events after dose 2 was similar to that seen with 16-25 year olds

• Adverse events overall were relatively few

• Highest incidence was in the General Disorders and Administration Site Conditions, reflecting 

local and systemic reactogenicity events 

• Lymphadenopathy was identified as related to vaccination

• There were no related SAEs

• No deaths were reported 

Overall safety conclusions for 12-15 year olds in the Phase 2/3 analysis
Worldwide Research, Development and Medical Confidential 26

• Immune response to Pfizer-BioNTech COVID-19 Vaccine in SARS-CoV-2 50% neutralizing titers 

in adolescents 12-15 years of age was noninferior to (and in fact exceeded) the immune response 

in young adults 16-25 years of age, which provides immunobridging for adolescents in pivotal 

Study C4591001. 

• In the adolescent group, efficacy analyses based on cases reported from at least 7 days after 

Dose 2 through the data cutoff date, the observed VE was 100% (95% CI: 75.3%, 100%) for 

individuals without evidence of prior SARS-CoV-2 infection before and during vaccination 

regimen, and 100% (2-sided 95% CI: 78.1%, 100%) for those with or without evidence of prior 

SARS-CoV-2 infection before and during vaccination regimen. 

• No severe cases were reported in the 12-15 years of age group as of the date cutoff date.

• Overall, these immunogenicity and efficacy data strongly support BNT162b2 use in adolescents 

12-15 years of age.

Immunogenicity & Efficacy Conclusions for 12-15 year olds in the Phase 2/3 

analysis