Final Clinical Study Report
Protocol B7451036

CLINICAL STUDY REPORT SYNOPSIS
Sponsor: Pfizer Inc.
Investigational Product: PF-04965842 (Abrocitinib)
Clinical Study Report Synopsis: Protocol B7451036
Protocol Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center
Study Investigating the Efficacy and Safety of PF-04965842 Co-Administered With
Background Medicated Topical Therapy in Adolescent Participants 12 to <18 Years of AgeWith Moderate-to-Severe Atopic Dermatitis
Investigators: Refer to Appendix 16.1.4.1 for a list of investigators involved in this study.
Study Centers: Refer to Appendix 16.1.4.1 for a list of sites involved in this study.
Publications Based on the Study: None.
Study Initiation Date: 18 February 2019
Study Completion Date: 08 April 2020
Report Date: 10 September 2020
Previous Report Date(s): Not Applicable
Phase of Development: Phase 3
Primary and Secondary Study Objectives and Endpoints:
Table S1. Study Objectives and Endpoints
Type
Primary
Efficacy

Secondary
Efficacy

Objectives

Endpoints

To assess the efficacy of
PF-04965842 compared withplacebo when co-administeredwith background medicatedtopical therapy in adolescentparticipants 12 to <18 years ofage with moderate-to-severe
atopic dermatitis (AD).

Co-primary endpoints:
 Response based on the Investigator’s Global
Assessment (IGA) score of clear (0) or almost
clear (1) (on a 5-point scale) and a reduction
from baseline of ≥2 points at Week 12;
 Response based on the Eczema Area andSeverity Index (EASI) ≥75% improvement frombaseline (EASI-75) at Week 12.

To evaluate the effect of
PF-04965842 co-administeredwith background medicatedtopical therapy on additional
efficacy endpoints and patientreported outcomes (PRO) overtime in adolescent participants

Key Secondary Endpoints:
 Response based on at least 4 points
improvement in the Peak Pruritis Numerical
Rating Scale (PP-NRS) from baseline at
Weeks 2, 4, and 12;
 Change from baseline in Pruritus and Symptoms
Assessment for Atopic Dermatitis (PSAAD)PFIZER CONFIDENTIAL
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Table S1. Study Objectives and Endpoints
Type

PROs

Objectives
12 to <18 years of age withmoderate-to-severe AD.

Endpoints
total score at Week 12.
Secondary Efficacy Endpoints:
 Response based on at least 4 points
improvement in the PP-NRS from baseline at allscheduled time points other than Weeks 2, 4 and
12; Time to achieve at least 4 points improvementin the PP-NRS from baseline;
 Response based on the EASI-75 at all scheduled
time points except Week 12;
 Response based on the IGA of clear (0) or
almost clear (1) and 2-point reduction frombaseline at all scheduled time points except
Week 12.
Other Efficacy Endpoints:
 Response based on a ≥50%, ≥90% and 100%
improvement in the EASI total score (EASI-50,
EASI-90 and EASI-100) at all scheduled time
points; Change from baseline and percent change frombaseline in the percentage body surface area
(BSA) affected at all scheduled time points;
 Response based on affected BSA <5% at
Week 12;
 Response based on a ≥50% and ≥75%
improvement in Scoring Atopic Dermatitis(SCORAD50, SCORAD75) from baseline at allscheduled time points; Percent change from baseline in EASI at allscheduled time points;
 Change from baseline and percent change frombaseline at all scheduled time points in
SCORAD total score and subjective
assessments of sleep loss; Percent change from baseline in PP-NRS at allscheduled time points;
 Week 12 corticosteroid-free days.
 Change from baseline at Week 12 in Children’s
Dermatology Life Quality Index (CDLQI) andat all other scheduled time points;
 Change from baseline at Week 12 in Hospital
Anxiety and Depression Scale (HADS) and at
all other scheduled time points;
 Change from baseline at Week 12 inPatient-Oriented Eczema Measure (POEM) andat all other scheduled time points;
 Change from baseline at Week 12 in Dermatitis
Family Impact (DFI) questionnaire;

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CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives and Endpoints
Type

Objectives







Safety Objective and Endpoints
SafetyTo evaluate the safety andtolerability of PF-04965842
co-administered withbackground medicated topicaltherapy in adolescentparticipants 12 to <18 years ofage with moderate-to-severe
AD.






Immunogenicity Sub-Study Objective and Endpoints
Immunogenicity To evaluate the effect of
PF-04965842 on the
immunogenicity to Tdap vaccine
in adolescent participants 12 to<18 years of age withmoderate-to-severe AD.

Pharmacokinetic (PK) Objective and Endpoints
PK
To evaluate the PK of
PF-04965842 in adolescentparticipants 12 to <18 years ofage with moderate-to-severeAD.



Endpoints
Change from baseline of Patient Global
Assessment (PtGA) at Week 12 and at all otherscheduled time points;
Change from baseline of EuroQol Quality ofLife 5 Dimension Youth Scale (EQ-5D-Y) at
Week 12 and at all other scheduled time points;
Change from baseline of Pediatric Functional
Assessment of Chronic Illness Therapy Fatigue
Scale (Peds-FACIT-F) at Week 12 and at allother scheduled time points;
Response based on achieving ≥2.5-point
improvement from baseline in the CDLQI score
at all scheduled time points;
Response based on the PtGA of clear (0) or
almost clear (1) (on a 5-point scale) and areduction from baseline of ≥2 points at allscheduled time points.
Incidence of treatment-emergent adverse event(TEAEs);Incidence of serious adverse event (SAEs);
Incidence of adverse event (AEs) leading todiscontinuation;
The incidence of clinical abnormalities andchange from baseline in clinical laboratory
values, electrocardiogram (ECG) measurements,and vital signs.
Fold increase from baseline at 4 weeks
post-vaccination in concentration of
immunoglobulin G (IgG) against:
 Tetanus toxoid;
 Diphtheria toxoid; Pertussis toxoid; Pertactin (PRN);
 Filamentous hemagglutinin (FHA); Fimbriae types 2 and 3 (FIM).
Plasma concentrations of PF-04965842 inadolescent participants 12 to <18 years of age
with moderate-to-severe AD.

METHODS
Study Design: This was a randomized, double-blind, placebo-controlled, parallel-group,
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CLINICAL STUDY REPORT SYNOPSIS
Phase 3 study to evaluate the efficacy and safety of abrocitinib in adolescent participants
12 to <18 years of age with moderate-to-severe AD. Participants were screened within
28 days prior to the first dose of study intervention to confirm study eligibility. A total of
287 participants were randomized globally from 99 sites in a 1:1:1 ratio to receive abrocitinib
once daily (QD) at 200 mg, 100 mg, or placebo for 12 weeks.
Diagnosis and Main Criteria for Inclusion: Participants who met the following criteria
were enrolled in this study:
Confirmed diagnosis of AD at the screening and baseline visits according to Hanafin
and Rajka criteria for AD.

Documentation of any of the following:

Inadequate response to treatment with medicated topical therapy for AD for atleast 4 consecutive weeks, within 6 months before the screening visit; orTreatment with systemic therapy for AD within 6 months before the screening
visit; orParticipant was a candidate for systemic therapy for AD.

NOTE: Medicated topical therapy was defined as a topical product that contained an
active pharmaceutical ingredient indicated for the treatment of AD (irrespective ofwhether it was an over-the-counter [OTC] or prescribed product).
Moderate-to-severe AD (must have fulfilled all of the following criteria: affected
BSA 10%, IGA 3, EASI 16, and PP-NRS 4 at the baseline visit).

During the last 7 days prior to Day 1, for the treatment of AD, the participant musthave used only non-medicated topical therapy (ie, emollient) at least twice daily,
without other active ingredients indicated to treat AD, or other additives which could
have affected AD (eg, hyaluronic acid, urea, ceramide or filaggrin degradation
products), with response to treatment remaining inadequate at baseline.

Body weight ≥25 kg.

Study Treatment: Abrocitinib was administered orally at doses of 100 mg or 200 mg given
QD for 12 weeks based on treatment assignment. In addition, one treatment group was
assigned to receive abrocitinib-matching placebo. Study drug information is provided inTable S2.

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Table S2. Study Drug Information
Investigational Product Description

Vendor Lot
Number

Pfizer Lot
NumberStrength/Potency

DosageForm

Placebo for PF-04965842 Round White
Film Coated Tablet (9 mm)
PF-04965842 100 mg Round White
Film Coated Tablet (DC)
Placebo for PF-04965842 Round White
Film Coated Tablet (9 mm)
PF-04965842 100 mg Round White
Film Coated Tablet (DC)PF-04965842 100 mg Round White
Film Coated Tablet (DC)
Placebo for PF-04965842 Round White
Film Coated Tablet (9 mm)

N/A

17-004645

0 mg

TabletN/A

18-001885

100 mgTabletN/A

17-003139

0 mg

TabletN/A

18-002731

100 mgTabletN/A

18-001886

100 mgTablet19-DP-00021

19-001255

0 mg

TabletEfficacy Evaluations:
The primary endpoints are:

IGA response: Response based on the IGA score of clear (0) or almost clear (1); and areduction from baseline of 2 points at Week 12.

EASI-75 response: Response based on the EASI 75% improvement from baseline(EASI-75) at Week 12.

The key secondary efficacy endpoints are:

Response based on 4 points improvement from baseline in the PP-NRS frombaseline at Weeks 2, 4, and 12.

Change from baseline in PSAAD total score at Week 12.

The secondary efficacy endpoints are:

Response based on at least 4 points improvement in the PP-NRS from baseline at allscheduled time points other than Weeks 2, 4 and 12.

Time to achieve at least 4 points improvement in the PP-NRS from baseline.

Response based on the EASI-75 at all scheduled time points except Week 12.

Response based on the IGA of clear (0) or almost clear (1) and 2-point reduction frombaseline at all scheduled time points except Week 12.

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Response based on a 50%, 90% and 100% improvement in the EASI total score(EASI-50, EASI-90 and EASI-100) at all scheduled time points.



Change from baseline and percent change from baseline in the percentage BSA
affected at all scheduled time points.

Response based on BSA <5% at Week 12.

Response based on a 50% and 75% improvement in SCORAD (SCORAD50,SCORAD75) from baseline at all scheduled time points.



Percent change from baseline in EASI at all scheduled time points.



Change from baseline and percent change from baseline at all scheduled time points
in SCORAD total score and subjective assessments of sleep loss.

Percent change from baseline in PP-NRS at all scheduled time points.



Week 12 corticosteroid-free days.

The PRO secondary endpoints are:

Change from baseline at Week 12 in CDLQI and at all other scheduled time points.



Change from baseline at Week 12 in HADS and at all other scheduled time points.



Change from baseline at Week 12 in POEM and at all other scheduled time points.



Change from baseline at Week 12 in DFI questionnaire.



Change from baseline of PtGA at Week 12 and at all other scheduled time points.



Change from baseline of EQ-5D-Y at Week 12 and at all other scheduled time points.



Change from baseline of Peds-FACIT-F at Week 12 and at all other scheduled time
points.



Response based on achieving ≥2.5-point improvement from baseline in the CDLQI
score at all scheduled time points.

Response based on the PtGA of clear (0) or almost clear (1) (on a 5-point scale) and areduction from baseline of ≥2 points at all scheduled time points.

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CLINICAL STUDY REPORT SYNOPSIS
Pharmacokinetic and Immunogenicity Sub-Study Evaluations:
PK: Blood samples (3 mL) to provide minimum 1 mL of plasma for PK analysis werecollected into appropriately labeled tubes containing dipotassium ethylenediaminetetraacetic
acid (K2EDTA) at Day 57 pre-dose and Day 85 post-dose. PK plasma specimens wereassayed for abrocitinib using validated analytical methods.
Immunogenicity Sub-Study: This sub-study was to evaluate the effect of abrocitinib on
immunogenicity to Tdap vaccine in adolescent participants.
Safety Evaluations: Safety evaluations included incidences of TEAEs, SAEs, AEs leading
to discontinuation, clinical abnormalities, ECG measurements, and vital signs.
Statistical Methods:
Efficacy: Abrocitinib 200 mg QD was declared superior to placebo if the null hypothesis of
no difference between abrocitinib 200 mg QD versus placebo for both co-primary endpoints
was rejected at the 5% significance level. Similarly, abrocitinib 100 mg QD was declared
superior to placebo if the null hypothesis of no difference between abrocitinib 100 mg QD
versus placebo for both co-primary endpoints was rejected at the significance level specified
below.
The familywise Type-I error rate for assessing the co-primary and key secondary endpoints
was strongly controlled at 5% (2-sided) using a sequential, Bonferroni-based iterative
multiple testing procedure.
The procedure first assessed the co-primary endpoints (IGA and EASI-75 at Week 12 for
200 mg QD versus placebo) at the 5% level. If this hypothesis was not rejected, then all
subsequent hypotheses was not considered statistically significant. If this hypothesis was
rejected, then assessing for statistical significance continued as follows:

The hypothesis for severity of pruritus (PP-NRS4) 200 mg QD versus placebo at
Week 2 was assessed at the 2.5% level. If this hypothesis was rejected, then theunused alpha level of 2.5% was passed on to the assessment for the key secondary
endpoints and the co-primary endpoints for 100 mg QD versus placebo, in the orderspecified in Sequence A at a 5% significance level. All subsequent hypotheses fromany point where a hypothesis cannot be rejected were not considered statisticallysignificant.



If the hypothesis for severity of pruritus (PP-NRS4) 200 mg QD versus placebo at
Week 2) was not rejected at the 2.5% level, then the hypotheses for the key secondary
endpoints and the co-primary endpoints for 100 mg QD versus placebo, in the orderspecified in Sequence A were assessed at a 2.5% significance level. If all hypotheses
in this sequence were rejected, then the unused alpha level of 2.5% was passed on to
the assessment of the hypothesis for severity of pruritus (200 mg QD versus placebo)
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CLINICAL STUDY REPORT SYNOPSIS
at Week 2 at the 5% level. All subsequent hypotheses from any point where ahypothesis cannot be rejected were not considered statistically significant.
Estimates of the pairwise differences along with its 2-sided 95% confidence interval (CI)were provided among the active treatment groups, abrocitinib 200 mg QD, abrocitinib 100
mg QD, and placebo.
PK: Plasma concentration data for abrocitinib were summarized through appropriate datatabulations, descriptive statistics and graphical presentation.
Immunogenicity Sub-Study: For the fold increase 4 weeks post-vaccination the ratio ofconcentration values was calculated. Ratio values were logarithmically transformed foranalysis purposes. The geometric mean fold rise (GMFR) of these fold rises was calculated
for each treatment arm.
Safety: All safety data were summarized descriptively through appropriate data tabulations,descriptive statistics, categorical summaries, and graphical presentations.
RESULTS
Subject Disposition and Demography:
A total of 408 participants were screened, and 287 subjects were randomized. There were2 participants who randomized to the abrocitinib 200 mg group were not treated.
The disposition events summary, including reasons for discontinuation, are presented inTable S3. Most participants completed Week 12 of the study; discontinuations were low at
3.2% to 6.3% across the treatment groups with highest proportion in the placebo group.
One participant lost to follow-up as a result of Corona Virus Disease 2019 (COVID-19)
impact.

Table S3. Disposition Events Summary - Safety Analysis Set

Number (%) of Subjects

Discontinued

Placebo(N=96)

PF-04965842
100mg QD
(N=95)

PF-04965842
200mg QD
(N=94)

n (%)

n (%)

n (%)

6 (6.3)3 (3.2)3 (3.2)Adverse Event

2 (2.1)1 (1.1)2 (2.1)

Lost to Follow-Up

2 (2.1)1 (1.1)

0

Protocol Deviation00

1 (1.1)PFIZER CONFIDENTIAL
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Table S3. Disposition Events Summary - Safety Analysis Set
Placebo(N=96)

PF-04965842
100mg QD
(N=95)

PF-04965842
200mg QD
(N=94)

n (%)

n (%)

n (%)

Withdrawal By Parent/Guardian

1 (1.0)1 (1.1)0

Other

1 (1.0)00Completed

90 (93.8)

92 (96.8)

91 (96.8)

Number (%) of Subjects

Completed means completed 12 weeks treatment.
PFIZER CONFIDENTIAL SDTM Creation: 12MAY2020 (11:13) Source Data: adds Output
File: ./nda1_cdisc/B7451036/adds_s001 Date of Generation: 18MAY2020 (23:38)
Table 14.1.1.2.1 is for Pfizer internal use.

Baseline demographic characteristics were balanced across treatment groups. The medianage was 15.0 years and there were 50.9% males. Majority of the participants were White(56.1%) and Asian (33.0%).
Baseline disease characteristics were balanced across treatment groups. Randomized
participants were representative of the moderate (61.4%) or severe (38.6%) AD population atbaseline per the IGA score; also, the median EASI was 25.6 and median %BSA was 45.5%.
The baseline PRO values were representative of a high burden of disease and impact on QoL.
Median CDLQI values were similar across groups, ranging from 13.0 to 14.0. Median POEM
values were also similar across groups, ranging from 20.0 to 21.0.
Efficacy Results:
Co-Primary Efficacy Endpoints:
The study met both co-primary endpoints of IGA and EASI-75 responses at Week 12,
demonstrating that both abrocitinib 100 mg and 200 mg treatment groups were superior to
the placebo group:

Statistically significantly higher proportion of participants achieved IGA responses
for abrocitinib 100 mg (p=0.0147) and 200 mg (p=0.0030) treatment groups
compared with the placebo group (Table S4).



Statistically significantly higher proportion of participants achieved EASI-75
responses for abrocitinib 100 mg (p=0.0002) and 200 mg (p<0.0001) treatmentgroups compared with the placebo group (Table S5).

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Table S4. Proportion of Subjects Achieving Investigator's Global Assessment (IGA)
Response of 'Clear' or 'Almost Clear' and >=2 Points Improvement fromBaseline at Week 12 - CMH (FAS, NRI)

N

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

94

89

93

n (%)

23 (24.5)

37 (41.6)

43 (46.2)

95% CI(15.8, 33.2)(31.3, 51.8)(36.1, 56.4)

16.7

20.6

(3.5, 29.9)(7.3, 33.9)

0.01470.0030

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

3.9

95% CI(-10.4, 18.2)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the measurement collected on or prior to Day 1.
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; N = number of subjects in the analysis set with NRI at the
specified visit; n (%) = number of subjects with response (percentage based on N); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference foreach randomization stratum using thenormal approximation of binomial proportions. The confidence interval for the response rate was based on normal
approximation (or the Clopper-Pearson exact method when there were no or if all were responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by randomization strata (baseline
disease severity).
PFIZER CONFIDENTIAL SDTM Creation: 12MAY2020 (11:16) Source Data: adad Output
File: ./nda1_cdisc/B7451036/adad_s102 Date of Generation: 18MAY2020 (22:18)
Table 14.2.1.1.1.1 is for Pfizer internal use.

Table S5. Proportion of Subjects Achieving Eczema Area and Severity Index (EASI)
Response >= 75% Improvement from Baseline at Week 12 - CMH (FAS,
NRI)

N

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

94

89

93

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Table S5. Proportion of Subjects Achieving Eczema Area and Severity Index (EASI)
Response >= 75% Improvement from Baseline at Week 12 - CMH (FAS,
NRI)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QDn (%)

39 (41.5)

61 (68.5)

67 (72.0)

95% CI(31.5, 51.4)(58.9, 78.2)(62.9, 81.2)

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]

26.5

29.4

(13.1, 39.8)(16.3, 42.5)

0.0002<.0001200 mg QD - 100 mg QD [1]Estimate (%)

3.1

95% CI(-9.9, 16.2)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the measurement collected on or prior to Day 1.
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; N = number of subjects in the analysis set with NRI at the
specified visit; n (%) = number of subjects with response (percentage based on N); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference foreach randomization stratum using thenormal approximation of binomial proportions. The confidence interval for the response rate was based on normal
approximation (or the Clopper-Pearson exact method when there were no or if all were responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by randomization strata (baseline
disease severity).
PFIZER CONFIDENTIAL SDTM Creation: 12MAY2020 (23:29) Source Data: adea Output
File: ./nda1_cdisc/B7451036/adea_s104 Date of Generation: 18MAY2020 (23:09)
Table 14.2.1.1.3.1 is for Pfizer internal use.

Key Secondary Efficacy Endpoints:
All subsequent hypotheses (after the comparison of PP-NRS4 for abrocitinib 100 mg versus
placebo at Week 4) were not considered statistically significant. Thus hypotheses (a)comparison of PP-NRS4 for abrocitinib 100 mg versus placebo at Week 12; and (b)comparison of change from baseline in the total PSAAD score for both abrocitinib doses
versus placebo at Week 12 were not considered statistically significant.
Abrocitinib 200 mg group had statistically significantly greater proportion of PP-NRS4
responders compared with the placebo group at Weeks 2, 4, and 12 (Table S6). Abrocitinib
100 mg group had statistically significantly greater proportion of PP-NRS4 responders
compared with the placebo group at Week 2, but not at Week 4 (Table S6).

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Table S6. Proportion of Subjects with >=4 Points at Baseline and Achieving >=4 Points
Improvement from Baseline in Numeric Rating Scale for Severity ofPruritus at Weeks 2, 4, 8 and 12 - CMH (FAS, NRI)

Week 2N

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

95

92

88

n (%)

12 (12.6)

25 (27.2)

34 (38.6)

95% CI(6.0, 19.3)(18.1, 36.3)(28.5, 48.8)

14.7

26.1

(3.5, 25.9)(13.9, 38.3)

0.0119<.0001

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

11.7

95% CI
Week 4N(-1.8, 25.2)
92

89

84

n (%)

19 (20.7)

28 (31.5)

42 (50.0)

95% CI(12.4, 28.9)(21.8, 41.1)(39.3, 60.7)

10.9

29.4

(-1.8, 23.6)(16.0, 42.9)

0.0971<.0001

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

18.4

95% CI
Week 8N(4.1, 32.7)
92

87

85

n (%)

29 (31.5)

36 (41.4)

48 (56.5)

95% CI(22.0, 41.0)(31.0, 51.7)(45.9, 67.0)

9.9

24.9

(-4.1, 23.9)(10.8, 39.0)

0.17230.0009Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

15.1

95% CI
Week 12N(0.4, 29.9)
84

76

74

n (%)

25 (29.8)

40 (52.6)

41 (55.4)

95% CI(20.0, 39.5)(41.4, 63.9)(44.1, 66.7)

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Table S6. Proportion of Subjects with >=4 Points at Baseline and Achieving >=4 Points
Improvement from Baseline in Numeric Rating Scale for Severity ofPruritus at Weeks 2, 4, 8 and 12 - CMH (FAS, NRI)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Active - Placebo [1]Estimate (%)
95% CI

22.8

25.6(8.0, 37.7)(10.6, 40.6)

0.00350.0013Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

2.6

95% CI(-13.4, 18.7)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the measurement collected on or prior to Day 1.
If a subject withdrew from the study, then this subject was counted as non-responder after withdrawal.
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; N = number of subjects in the analysis set with NRI at the
specified visit; n (%) = number of subjects with response (percentage based on N); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of difference foreach randomization stratum using thenormal approximation of binomial proportions. The confidence interval for the response rate was based on normal
approximation (or the Clopper-Pearson exact method when there were no or if all were responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by randomization strata (baseline
disease severity).
PFIZER CONFIDENTIAL SDTM Creation: 12MAY2020 (11:17) Source Data: adnr2 Output
File: ./nda1_cdisc/B7451036/adnr_s201 Date of Generation: 18JUN2020 (22:02)
Table 14.2.3.2.1.1 is for Pfizer internal use.

Other Secondary Efficacy Endpoints:
Remaining secondary efficacy endpoints (not multiplicity controlled) showed similar patternof efficacy as the primary and key efficacy endpoints. Efficacy with both abrocitinib groups
was statistically significantly better (not controlled for multiplicity) than placebo for all
secondary endpoints.
PP-NRS:
The proportions of PP-NRS4 responders at Day 2 to Day 15 and Week 8 were all
numerically greater in the abrocitinib 200 mg and 100 mg groups than the placebo group, but
the differences did not reach statistical significance at some timepoints.
The Kaplan-Meier analysis to estimate the time to first PP-NRS4 showed the time toresponse was statistically significantly faster in the abrocitinib 100 mg (p=0.0159) and
200 mg (p=0.0003) groups compared with the placebo group. Since response was assessed
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only at scheduled visits after Week 2, it was unknown whether the actual median time toresponse was between 2 scheduled visits.
The least square mean (LSM) of percent change from baseline in PP-NRS was statisticallysignificantly improved (lower) in both abrocitinib 100 mg and 200 mg groups compared withthe placebo group at all scheduled time points except abrocitinib 200 mg versus placebo at
Day 2 and both abrocitinib groups versus placebo at Day 5.
IGA:
At Weeks 4 and 8, both abrocitinib treatment groups showed statistically significantly higher
proportions of participants with IGA responses compared with the placebo group. At
Week 2, only abrocitinib 200 mg group showed statistically significantly higher proportionsof participants with IGA responses compared with the placebo group.
EASI:
Both abrocitinib treatment groups had statistically significantly greater proportion of
EASI-75 responders compared with the placebo group at Weeks 2, 4, and 8.
The LSM of percent change from baseline in the total EASI score demonstrated statisticallysignificant decreases in both abrocitinib treatment groups compared with the placebo groupat all scheduled time points (Weeks 2, 4, 8, and 12).
Both abrocitinib treatment groups demonstrated statistically significantly greater EASI-50
and EASI-90 responses compared with the placebo group at all scheduled time points(Weeks 2, 4, 8, and 12). At Week 2, only 1 participant from abrocitinib 100 mg group
achieved EASI-100 response and none from the placebo or abrocitinib 200 mg group
achieved EASI-100 response. Abrocitinib 200 mg group demonstrated statisticallysignificantly greater EASI-100 responses compared with the placebo group only at Weeks 4
and 8.
BSA:
Both abrocitinib treatment groups demonstrated statistically significant decreases frombaseline in %BSA compared with the placebo group as early as Week 2 and were maintainedat Weeks 4, 8, and 12 (p ≤ 0.0001 for absolute change and p ≤ 0.0002 for percent change,
based on the MMRM analysis).
Statistically significantly higher proportions of participants achieved %BSA < 5% for both
abrocitinib treatment groups compared with the placebo group (p < 0.05) except forabrocitinib 200 mg group at Week 12.
SCORAD:PFIZER CONFIDENTIAL
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Both abrocitinib treatment groups demonstrated statistically significantly higher proportionsof participants with SCORAD50 responses compared with the placebo group as early as
Week 2 (p ≤ 0.0089) and were maintained at each scheduled time point up to Week 12(p < 0.0001).
Both abrocitinib treatment groups demonstrated statistically significantly higher proportionsof participants with SCORAD75 responses compared with the placebo group as early as
Week 2 (p ≤ 0.0242) and were maintained at each scheduled time point up to Week 12,
except abrocitinib 100 mg group at Week 8.
Both abrocitinib treatment groups demonstrated statistically significantly greater decreases
compared with the placebo group in absolute value (p < 0.0001 for both abrocitinib treatmentgroups) and percent change from baseline (p ≤ 0.0003) of SCORAD total score, began at
Week 2 and were maintained at each scheduled time point up to Week 12, based on the
MMRM analysis.
Both abrocitinib treatment groups demonstrated statistically significantly greater decreases
compared with the placebo group in absolute value change from baseline in SCORAD Visual
Analogue Scale (VAS) of sleep loss, that began at Week 2 and were maintained at eachscheduled time point up to Week 12.
Corticosteroid-Free Days:
LSM of number of days up to Week 12 when corticosteroid was not used was statisticallysignificantly higher in the abrocitinib 200 mg group compared with the placebo group(p=0.0176).
Patient-Reported Outcomes Endpoints:
CDLQI
The LSM of change from baseline in CDLQI scores was statistically significantly improved(lower than baseline) in both abrocitinib treatment groups compared with the placebo groupat Weeks 2, 4, 8, and 12.
Proportion of participants with ≥2.5-point improvement from baseline in the CDLQI score in
the abrocitinib 100 mg treatment group showed statistically significant difference from theplacebo group at Weeks 8 and 12.

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The LSM changes from baseline in HADS anxiety subscale did not show statisticallysignificant improvement (lower) for both abrocitinib treatment groups compared with theplacebo group at Weeks 2, 4, 8 and 12.
The LSM changes from baseline in HADS depression subscale did not show statisticallysignificant improvement (lower) for both abrocitinib treatment groups compared with theplacebo group at Weeks 2, 4, 8 and 12.
POEM
The LSM of change from baseline in POEM scores was statistically significantly improved(lower than baseline) in both abrocitinib treatment groups compared with the placebo groupat Weeks 2, 4, 8, and 12 (p < 0.0001).
DFI Questionnaire
At Week 12, LSM of change from baseline in DFI score was statistically significantly
improved (lower than baseline) in abrocitinib 200 mg group compared with the placebogroup.
PtGA
The LSM of change from baseline in PtGA scores was statistically significantly improved(lower) for both abrocitinib treatment groups compared with the placebo group that began at
Week 2 and were maintained up to Week 12.
Both abrocitinib treatment groups demonstrated statistically significantly higher proportionsof participants with ≥2 points at baseline and achieving ‘Clear’ or ‘Almost Clear’ and≥2 points improvement from baseline in PtGA compared with the placebo group that began
at Week 4 and were maintained up to Week 12.
EQ-5D-Y
The LSM of change from baseline in EQ-5D-Y scores was statistically significantly
improved (higher) for abrocitinib 200 mg group compared with the placebo group at Weeks
2, 4, 8 and 12; and for abrocitinib 100 mg group compared with the placebo group at Week 8.
Peds-FACIT-F
The LSM changes from baseline in Peds-FACIT-F at Week 12 did not show statisticallysignificant improvement for both abrocitinib treatment groups compared with the placebogroup.
Pharmacokinetic and Immunogenicity Sub-Study Results:
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The mean plasma abrocitinib concentrations observed at 2 hours prior to dosing (Week 8)
and at 2 hours post dose (Week 12) appeared to increase in a dose-related manner between
the abrocitinib 200 mg and 100 mg QD groups in this study.
Immunogenicity Sub-Study
Immunogenicity sub-study analysis set was defined as participants who had completed
8 weeks of treatment and received Tdap vaccination. All participants (10, 9, 6 participants inthe placebo group, abrocitinib 100 mg and 200 mg groups, respectively) in the
immunogenicity sub-study completed the 12 weeks treatment.
Greater than 4-fold increase in pertussis toxin IgG and tetanus toxoid IGG antibody wasobserved in the abrocitinib group. There was no apparent difference on immunogenicity toTdap vaccine between abrocitinib and placebo.
Safety Results:
No deaths were reported in the study.
The proportion of participants with all-causality TEAEs was higher for the abrocitinib
200 mg group (62.8%) compared to the abrocitinib 100 mg (56.8%) and placebo (52.1%)
groups (Table S7). Three participants reported SAEs (2 from the placebo group and 1 fromthe abrocitinib 200 mg group; Table S7), and no SAEs were treatment-related.
Note: There were 2 TEAEs (hand fracture in the abrocitinib 100 mg group, pustule in theplacebo group) missing in Table S7, both TEAEs were not treatment-related and had no
substantive impact on efficacy and/or safety interpretation as well as on the statisticalconclusions for this study.
The proportion of participants experiencing severe AEs and AEs leading to study
discontinuations or temporary discontinuations were low and similar across all treatmentgroups.

Table S7. Treatment-Emergent Adverse Events (All Causalities, Safety Analysis Set)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Number (%) of Subjects

n (%)

n (%)

n (%)

Subjects evaluable for adverse events

96

95

94

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Table S7. Treatment-Emergent Adverse Events (All Causalities, Safety Analysis Set)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Number (%) of Subjects

n (%)

n (%)

n (%)

Number of adverse events

99

134

132

Subjects with adverse events

50 (52.1)

54 (56.8)

59 (62.8)

Subjects with serious adverse events

2 (2.1)0

1 (1.1)

Subjects with severe adverse events

2 (2.1)0

2 (2.1)

Subjects discontinued from study due to adverse events [1]2 (2.1)1 (1.1)2 (2.1)

Subjects discontinued study drug due to AE and continue Study [2]Subjects with temporary discontinuation from study drug due to adverse
events000

4 (4.2)4 (4.2)4 (4.3)

Included data up to 28 days after last dose of study.
Except for the number of adverse events subjects were counted only once per treatment in each row.
Serious Adverse Events - according to the investigator's assessment.
[1] Subjects who had an AE record that indicated that the AE caused the subject to be discontinued from the study[2] Subjects who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did notcause the subject to be discontinued from Study
MedDRA v23.0 coding dictionary applied.
PFIZER CONFIDENTIAL SDTM Creation: 13MAY2020 (01:35) Source Data: adae Output
File: ./nda1_cdisc/B7451036/adae_s010 Date of Generation: 20MAY2020 (01:33)
Table 14.3.1.2.1.1 is for Pfizer internal use.

There were no reported serious infections, pulmonary embolism, malignancies, major
adverse cardiovascular event (MACE) or venous thromboembolic event (VTE) in this study.
The most frequently reported system organ class (SOC) was Infections and Infestations, withslightly higher proportion of participants reported in the abrocitinib 200 mg (36.2%) and
100 mg (35.8%) groups compared with the placebo group (31.3%).
Only 1 participant in the abrocitinib 100 mg group experienced a Tier-1 event of herpes
zoster and the event was mild in severity.
There were no clinically significant hematologic parameters except for platelet which has adose-dependent decrease in abrocitinib groups with nadir at Week 4; majority of participantsremained within the normal range.
No clinically meaningful increases in total cholesterol and low-density lipoprotein (LDL)cholesterol (reached a plateau since Week 4) were observed in this study. There were noclinically meaningful changes in the LDL/high-density lipoprotein (HDL) ratio in any
treatment groups at Week 4 or Week 12.

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Compared with the placebo group, there were dose-dependent increases of creatine kinase inabrocitinib treatment groups.
No clinically significant changes or pattern in the abrocitinib treatment groups were observedin vital signs and ECG data.
Conclusions:
Efficacy
Co-Primary Endpoints:

The study met both co-primary endpoints of IGA and EASI-75 responses at Week 12,
demonstrating that both abrocitinib 100 mg and 200 mg treatment groups were superior
to the placebo group.
o Statistically significantly higher proportions of participants achieved IGA responses
and EASI-75 responses for both abrocitinib treatment groups compared with theplacebo group.
o Sensitivity analyses of IGA and EASI-75 responses were consistent with the primary
analyses.
o The treatment effects for both IGA response and EASI-75 response were similar
across subgroups.

Key Secondary Endpoints:

Abrocitinib 200 mg group had statistically significantly greater proportions of PP-NRS4
responders compared with the placebo group at Weeks 2, 4, and 12.



Abrocitinib 100 mg group had statistically significantly greater proportion of PP-NRS4
responders compared with the placebo group at Week 2, but not at Week 4.

Comparison of PP-NRS4 for abrocitinib 100 mg versus placebo at Week 12, andcomparison of change from baseline in the total PSAAD score for both abrocitinib doses
versus placebo at Week 12 were not considered statistically significant.

Other Secondary Endpoints:
Additional secondary efficacy endpoints (IGA, EASI, PP-NRS, BSA, SCORAD, andcorticosteroid-free days) generally demonstrated improved efficacy in abrocitinib groups
compared with the placebo group, especially for the abrocitinib 200 mg group.

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PP-NRS:The proportions of PP-NRS4 responders from Day 2 to Day 15 and at Week 8 were all
numerically greater in the abrocitinib 200 mg and 100 mg groups than in the placebogroup.

Time to first PP-NRS4 showed the time to response was statistically significantly fasterin the abrocitinib 100 mg (p=0.0159) and 200 mg (p=0.0003) groups compared with theplacebo group.



The LSM of percent change from baseline in PP-NRS was statistically significantly
improved (lower) in both abrocitinib 100 mg and 200 mg groups compared with theplacebo group at all scheduled time points except abrocitinib 200 mg versus placebo at
Day 2 and both abrocitinib groups versus placebo at Day 5 and Day 7.

IGA:

At Weeks 4 and 8, both abrocitinib treatment groups showed statistically significantly
higher proportions of participants with IGA responses compared with the placebo group.
At Week 2, only abrocitinib 200 mg group showed statistically significantly higher
proportions of participants with IGA responses compared with the placebo group.

Abrocitinib 200 mg group had a greater proportion of IGA responders than the
abrocitinib 100 mg group at Weeks 4 and 8.

EASI:


Statistically significantly greater EASI-50, EASI-75, and EASI-90 responses for both
abrocitinib treatment groups compared with the placebo group were observed at allscheduled timepoints (Weeks 2, 4, 8, and 12) except EASI-75 at Week 12.

The LSM of percent change from baseline in the total EASI score demonstrated
statistically significant decreases in both abrocitinib treatment groups compared with theplacebo group at Weeks 2, 4, 8, and 12.



Abrocitinib 200 mg group demonstrated statistically greater EASI-100 responses
compared with the placebo group only at Weeks 4 and 8.

BSA:Both abrocitinib treatment groups demonstrated statistically significant decreases frombaseline in %BSA compared with the placebo group as early as Week 2 and weremaintained at Weeks 4, 8 and 12.

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Statistically significantly higher proportions of participants achieved %BSA < 5% forboth abrocitinib treatment groups compared with the placebo group except for abrocitinib
200 mg group at Week 12.

SCORAD:

Both abrocitinib treatment groups demonstrated statistically significantly higher
proportions of participants with SCORAD50 responses compared with the placebo groupas early as Week 2 and were maintained at each scheduled time point up to Week 12.

Both abrocitinib treatment groups demonstrated statistically significantly higher
proportions of participants with SCORAD75 responses compared with the placebo groupas early as Week 2 and were maintained at each scheduled time point up to Week 12,
except abrocitinib 100 mg group at Week 8.

Both abrocitinib treatment groups demonstrated statistically significantly greater
decreases compared with the placebo group in absolute value and percent change frombaseline of SCORAD total score, that began at Week 2 and were maintained at eachscheduled time point up to Week 12.

Both abrocitinib treatment groups demonstrated statistically significantly greater
decreases compared with the placebo group in absolute value change from baseline in
SCORAD VAS of sleep loss, that began at Week 2 and were maintained at eachscheduled time point up to Week 12.

Corticosteroid-Free Days:

Number of days up to Week 12 when corticosteroid was not used was statisticallysignificantly higher in the abrocitinib 200 mg group compared with the placebo group.

Patient-Reported Outcomes:
Favorable and improved differences across most PRO measures (CDLQI, POEM, DFI,
PtGA, and EQ-5D-Y) were observed for abrocitinib treatment groups compared with theplacebo group, except for HADS and Peds-FACIT-F.


CDLQI: change from baseline in CDLQI scores was statistically significantly improved(lower than baseline) in both abrocitinib treatment groups compared with the placebogroup at Weeks 2, 4, 8, and 12. Participants with ≥ 2.5-point improvement from baselinein the CDLQI score in abrocitinib 100 mg treatment group showed statistically significant
difference from the placebo group at Weeks 8 and 12.



HADS: changes from baseline in HADS anxiety and depression subscales did not show
improvement (lower) for either abrocitinib treatment groups compared with the placebogroup at Weeks 2, 4, 8, and 12.
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POEM: change from baseline in POEM scores was statistically significantly improved(lower than baseline) in both abrocitinib treatment groups compared with the placebogroup at Weeks 2, 4, 8, and 12.



DFI Questionnaire: at Week 12, change from baseline in DFI score was statisticallysignificantly improved (lower than baseline) in abrocitinib 200 mg group compared withthe placebo group.



PtGA: changes from baseline in PtGA scores was statistically significantly improved(lower) for both abrocitinib treatment groups compared with the placebo group that began
at Week 2 and were maintained up to Week 12.

EQ-5D-Y: change from baseline in EQ-5D-Y scores was statistically significantly
improved (higher) for abrocitinib 200 mg group compared with the placebo group at
Weeks 2, 4, 8, and 12.



Peds-FACIT-F: changes from baseline in Peds-FACIT-F at Week 12 did not show
statistically significant improvement for either abrocitinib treatment groups comparedwith the placebo group.

Pharmacokinetics
The mean plasma abrocitinib concentrations observed at 2 hours prior to dosing (Week 8)
and at 2 hours post-dose (Week 12) appeared to increase in a dose-related manner
between the abrocitinib 200 mg and 100 mg QD groups in this study.

Safety

Abrocitinib was well tolerated. The observed safety events were consistent with thoseseen in other abrocitinib studies.

A higher incidence of AEs was reported in the abrocitinib groups, however, thepercentage of participants experiencing SAEs, severe AEs and AEs leading to study
discontinuation were low and similar across treatment groups.



No serious infections were reported in this study.



Infections and Infestations were the most frequently reported AEs across all treatmentgroups.



A higher incidence of nausea and herpes simplex infections were observed in the
abrocitinib groups. Only 1 event of herpes zoster was reported in the abrocitinib 100 mg
group.

No cases of MACE were observed in the study.
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No deaths or VTE were reported in the study.

No participants discontinued treatment due to thrombocytopenia and/or lymphopenia
according to protocol-specified discontinuation criteria.



Dose-dependent decrease in platelets in abrocitinib groups with nadir at Week 4; themajority of participants remained within the normal range.

No clinically significant changes in hemoglobin, lymphocyte and neutrophil counts.



No clinically meaningful increases in total cholesterol and LDL cholesterol (reached aplateau since Week 4); LDL:HDL ratios in both abrocitinib groups were unchanged
through Week 12.

Dose-dependent increases in creatine kinase were observed, no rhabdomyolysis wasreported.

No pattern of concern in ECG, vital signs and no unexpected laboratory abnormalities
were observed.

No unique safety signals were noted in the study.

Immunogenicity Sub-Study

There was no apparent difference on immunogenicity to Tdap vaccine between
abrocitinib and placebo. Greater than 4-folder increase in pertussis toxin IgG and tetanus
toxoid IGG antibody was observed in the abrocitinib groups. A clinically meaningfulconclusion cannot be established because of the small sample size.

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