Final Clinical Study Report
Protocol B7451029

CLINICAL STUDY REPORT SYNOPSIS
Sponsor: Pfizer, Inc.
Investigational Product: Abrocitinib (PF-04965842)
Clinical Study Report Synopsis: Protocol B7451029
Protocol Title: A Phase 3 Randomized, Double-Blind, Double-Dummy, PlaceboControlled, Parallel Group, Multi-Center Study Investigating the Efficacy and Safety of
PF-04965842 and Dupilumab in Comparison With Placebo in Adult Subjects on Background
Topical Therapy, With Moderate to Severe Atopic Dermatitis
Investigators: Refer to Appendix 16.1.4.1 for a list of investigators involved in this study.
Study Center(s): 194 sites in 18 countries, United States (n=46), Poland (n=36), Republicof Korea (n=7), Japan (n=12), Australia (n=10), Bulgaria (n=5), Canada (n=11), Germany(n=13), United Kingdom (n=11), Latvia (n=5), Hungary (n=5), Czech Republic (n=7), Chile(n=4), Spain (n=5), Italy (n=2), Mexico (n=4), Slovakia (n=5), and Taiwan (n=6). Refer toAppendix 16.1.4.1 for a list of sites involved in this study.
Publications Based on the Study: None
Study Initiation Date: First Subject First Visit: 29 OCT 2018
Study Completion Date: Last Subject Last Visit: 06 MAR 2020;
Primary Completion Date: 27 DEC 2019
Report Date: 28 May 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
Objective
Primary
Efficacy  To compare the efficacy of
100 mg and 200 mg once daily(QD) of PF-04965842 versus
placebo in adult subjects on
background topical therapy
with moderate to severe atopic
dermatitis (AD).

Endpoint
 Response based on achieving the Investigator's
Global Assessment (IGA) of clear (0) or almost clear(1) (on a 5-point scale) and a reduction from baseline(pre-dose Day 1) of 2 points at Week 12.
 Response based on achieving the Eczema Area andSeverity Index (EASI)-75 (75% improvement frombaseline) at Week 12.

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CLINICAL STUDY REPORT SYNOPSIS
Secondary
Efficacy  To compare the efficacy of
PF-04965842 versus
dupilumab in terms ofattaining a clinicallysignificant improvement in
the severity of pruritus for
adult subjects on background
topical therapy with moderate
to severe AD.
 To estimate the difference inefficacy measures between
two doses of PF-04965842
and dupilumab for adultsubjects on background
topical therapy with moderate
to severe AD.
Efficacy  To estimate the effect of
PF-04965842 on additional
efficacy endpoints andpatient-reported outcomesover time in adult subjects on
background topical therapy
with moderate to severe AD.

Key Secondary Endpoint Response based on achieving at least 4 points
improvement in the severity of Pruritus Numerical
Rating Scale (NRS) from baseline at Week 2.

Key Secondary Endpoints
 Response based on achieving the IGA of clear (0) or
almost clear (1) (on a 5-point scale) and a reduction
from baseline of 2 points at Week 16.
 Response based on achieving EASI-75 (75%
improvement from baseline) at Week 16.
Secondary Efficacy Endpoints
 Response based on achieving the IGA of clear (0) or
almost clear (1) (on a 5-point scale) and 2-point
reduction from baseline at all scheduled time points
except Week 12 and Week 16.
 Response based on achieving a 75% improvementin the EASI total score (EASI-75) at all scheduled
time points except Week 12 and Week 16.
 Response based on achieving a 50%, 90%, and100% improvement in the EASI total score(EASI-50, EASI-90, and EASI-100) at all scheduled
time points.
 Response based on achieving at least 4 points
improvement in the severity of Pruritus NRS frombaseline at all scheduled time points except Week 2.
 Time from baseline to achieve at least 4 points
improvement in the severity of Pruritus NRS scale.
 Change from baseline in the percentage Body
Surface Area (BSA) affected at all scheduled time
points.
 Change from baseline of Patient Global Assessment(PtGA) at all scheduled time points.
 Change from baseline in Dermatology Life Quality
Index (DLQI) at all scheduled time points.
 Change from baseline in EuroQol Quality of Life
5-Dimension 5-Level Scale (EQ-5D-5L) at allscheduled time points.
 Change from baseline in Hospital Anxiety andDepression Scale (HADS) at all scheduled time
points.

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CLINICAL STUDY REPORT SYNOPSIS

Safety To compare the safety andtolerability of 100 mg and
200 mg QD of PF-04965842
and dupilumab versus placebo
in adult subjects on
background topical therapy
with moderate to severe AD.
 To estimate the safety andtolerability of the two dosesof PF-04965842 versus
dupilumab, for adult subjects
on background topical therapy
with moderate to severe AD.

 Change from baseline in Patient Oriented Eczema
Measure (POEM) at all scheduled time points.
 Change from baseline in Pruritus and Symptoms
Assessment for Atopic Dermatitis (PSAAD) total
score at all scheduled time points.
 Response based on a 50% and 75% improvementin Scoring Atopic Dermatitis (SCORAD50,SCORAD75) from baseline at all scheduled time
points.
 Change from baseline at all scheduled time points in
SCORAD subjective assessments of itch and sleep
loss.
 Steroid free days at Week 16.
 Incidence of treatment-emergent adverse event(AE)s.
 Incidence of serious adverse event (SAE)s and AEs
leading to discontinuation.
 Incidence of clinical abnormalities and change frombaseline in clinical laboratory values,
electrocardiogram (ECG) measurements, and vital
signs.

METHODS
Study Design: This was a randomized, double-blind, double-dummy, placebo-controlled,parallel-group, multi-center study to assess the efficacy and safety of abrocitinib 100 mg or
200 mg QD and dupilumab (as per label) compared with placebo in adult subjects on
background topical therapy, with moderate to severe AD. The treatment duration was
20 weeks. A total of 838 subjects were randomized from 194 sites globally. There was a
primary efficacy assessment at Week 12, and key secondary efficacy assessments at Week 2
and Week 16. Efficacy and safety endpoints were assessed throughout the entire study.
Diagnosis and Main Criteria for Inclusion: Subjects aged 18 years or older at the time of
informed consent and met following AD criteria were enrolled:Clinical diagnosis of chronic AD for at least 1 year prior to Day 1 and had confirmed AD(Hanifin and Rajka criteria) at the screening and baseline visits.

Documented recent history (within 6 months before the screening visit) of inadequate
response to treatment with medicated topical therapy for AD for at least 4 weeks, or who
had required systemic therapies for control of their disease. Medicated topical therapy
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Protocol B7451029

CLINICAL STUDY REPORT SYNOPSIS
was defined as a topical product containing an active pharmaceutical ingredient indicatedfor the treatment of AD, irrespective of whether it is an over the counter or prescribed
product.
Moderate to severe AD (affected BSA 10%, IGA 3, EASI 16, and Pruritus NRS
severity score 4 on the day of the baseline visit).

During the 7 days prior to Day 1, the subject must have used only non-medicated topicaltherapy without other active ingredients indicated to treat AD, or other additives which
could affect AD at least twice daily, with response to treatment remaining inadequate atbaseline.

Study Treatment: Blinded abrocitinib, 100 mg tablets, and its matched placebo tablets were
provided in separate bottles. Subjects were dispensed two bottles of tablets, depending on
the study group, and were given clear dosing instructions to take one tablet from each bottle,
once daily (Table S2).
Blinded dupilumab, 300 mg/2 mL, and its matching placebo were provided as prefilled
syringes for subcutaneous injection. Two subcutaneous injections (loading dose of 600 mg
or placebo) were administered at baseline and one subcutaneous injection was administered
every 2 weeks (Q2W) as per the protocol Schedule of Activities.
Table S2. Investigational Product Description
Investigational Product Description

Vendor Lot
Number

Pfizer Lot
NumberStrength/
Potency

DosageForm

Placebo for Dupilumab 300 mg/2.0 ml Pre-Filled
2.25 ml Syringe Barrel
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)
Dupilumab 300 mg/2 ml single-dose prefilled
syringe with needle shield
Dupilumab 300 mg/2 ml single-dose prefilled
syringe with needle shield
PF-04965842 100 mg Round White Film Coated
Tablet (DC)Dupilumab 300 mg/2 ml single-dose prefilled
syringe with needle shield
Dupilumab 300 mg/2 ml single-dose prefilled
syringe with needle shield

3-FIN-3168

18-002278

0 mg/ml

GR-SDM

18-002727

0 mg

Prefillsyringe
TabletGR-SDM

18-002731

100 mgTabletGR-SDM

18-001886

100 mgTabletGR-SDM

17-003139

0 mg

Tablet

8L067A

18-003068

300 mg

8L310A

18-003459

300 mgGR-SDM

18-001885

100 mgCommercial
product
Commercial
product
Tablet

8L244A

18-002973

300 mg

7L616A

18-001641

300 mgPFIZER CONFIDENTIAL
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Commercial
product
Commercial
product

Final Clinical Study Report
Protocol B7451029

CLINICAL STUDY REPORT SYNOPSIS
Table S2. Investigational Product Description
Investigational Product Description

Vendor Lot
Number

Pfizer Lot
NumberStrength/
Potency

DosageForm

Dupilumab 300 mg/2 ml single-dose prefilled
syringe with needle shield
Placebo for Dupilumab 300 mg/2.0 ml Pre-Filled
2.25 ml Syringe Barrel

8L926A

19-001382

300 mg3-FIN-3414

19-001544

0 mg/ml

Commercial
product
Prefillsyringe

Efficacy Evaluations:Co-primary endpoints:
Response based on the IGA score of clear (0) or almost clear (1); and a reduction frombaseline of ≥2 points at Week 12;Response based on the EASI ≥75% improvement from baseline (EASI-75) at Week 12.

Key secondary efficacy endpoints:
Response based on ≥4 points improvement from baseline in the peak pruritis NRS (PPNRS4) for severity at Week 2;

Response based on achieving the IGA of clear (0) or almost clear (1) (on a 5-point scale)and a reduction from baseline of ≥2 points at Week 16;

Response based on achieving EASI-75 (≥75% improvement from baseline) at Week 16.

Secondary efficacy endpoints:
Response based on achieving the IGA of clear (0) or almost clear (1) (on a 5-point scale)and 2 point reduction from baseline at all scheduled time points except Week 12 andWeek 16;

Response based on achieving a 75% improvement in the EASI total score (EASI-75) atall scheduled time points except Week 12 and Week 16;

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

Percent change from baseline in total EASI score (included in the SAP, not in the
protocol);

Response based on achieving NRS4 at all scheduled time points except Week 2;
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Time from baseline to achieve NRS4;

Percent change from baseline in severity of PP-NRS each day from Days 2-15, Weeks 4,
8, 12, and 16 (included in the statistical analysis plan [SAP], not in the protocol);

Change from baseline and percent change from baseline in the percentage body surface
area (%BSA) affected at all scheduled time points;

Steroid-free days by Week 16;

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

Percent change from baseline and change from baseline at all scheduled time points in the
SCORAD total score;Percent change from baseline and change from baseline at all scheduled time points in
SCORAD subjective assessments of sleep loss.

Patient Reported Outcomes (PRO) secondary endpoints:


Change from baseline of PtGA at all scheduled time points;



Change from baseline in DLQI at all scheduled time points;



Change from baseline in EQ-5D-5L at all scheduled time points;



Change from baseline in each component (anxiety and depression) of the HADS at allscheduled time points;



Change from baseline in POEM at all scheduled time points;



Change from baseline in PSAAD total score at all scheduled time points.

Pharmacokinetic, Pharmacodynamic, and Pharmacogenomic Evaluations: Theseevaluations were not conducted in this study.
Safety Evaluations: Safety was assessed by the spontaneous reporting of AEs, physicalexaminations, vital signs, and clinical laboratory results in all subjects who received at least
1 dose of the investigational product. The safety endpoints included incidence of treatmentemergent AEs (TEAEs), incidence of SAEs and AEs leading to discontinuation, andincidence of clinical abnormalities and change from baseline in selected clinical laboratory
values, ECG measurements, and vital signs.

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CLINICAL STUDY REPORT SYNOPSIS
Statistical Methods: 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 coprimary 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 thesignificance level specified below.
A sequential Bonferroni-based iterative multiple testing procedure to strongly control thefamilywise Type 1 error at 5% was used for assessing each of the two abrocitinib doses(200 mg QD and 100 mg QD) versus placebo on the primary and key secondary endpoints.
The procedure belongs to a class of consonant multiple test procedures which are a subclassof the closed test procedures.
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, thenstatistical significance was not claimed for any subsequent hypotheses. If this hypothesis
was rejected, assessing for statistical significance continued for the co-primary endpoints(IGA and EASI-75 at Week 12) for the 100 mg QD versus placebo comparison. If thishypothesis was not rejected, then no statistical significance was claimed for any subsequent
hypotheses. If this hypothesis was rejected, then assessments continued as follows:
1. A series of hypotheses related to the severity of pruritus (NRS4) at Week 2 were assessedat the 2.5% level in the following order (Sequence A): 200 mg abrocitinib versus placebo,
100 mg abrocitinib versus placebo, 200 mg abrocitinib versus dupilumab, 100 mg
abrocitinib versus dupilumab.
2. If all hypotheses in Sequence A were rejected, then the unused alpha level of 2.5% was
passed on to the assessing for the Week 16 endpoints at a 5% significance level in thefollowing order (Sequence B): IGA, 200 mg abrocitinib versus placebo; EASI-75, 200
mg abrocitinib versus placebo, IGA, 100 mg abrocitinib versus placebo; EASI-75, 100
mg abrocitinib versus placebo. The statistical significance for each hypothesis in
Sequence B could not be claimed unless the prior hypothesis in the sequence wasstatistically significant. In Sequence B, if one hypothesis was not rejected at alpha levelof 5% then no statistical significance was claimed for any subsequent hypotheses in thesequence.
3. In Sequence A, if one hypothesis was not rejected at alpha level of 2.5% then no
statistical significance was claimed for any subsequent hypotheses in the sequence. In
this case, the assessing for statistical significance in Sequence B was at the 2.5% level. If
all hypotheses in Sequence B were rejected, then the unused alpha level of 2.5% was
passed back for assessing the hypotheses in Sequence A at the 5% level. In Sequence B,
if one hypothesis was not rejected at alpha level of 2.5 % then no statistical significancewas claimed for any subsequent hypotheses in the sequence.

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CLINICAL STUDY REPORT SYNOPSIS
After statistical significance was demonstrated at Week 2, in order to be more rigorous about
the onset of relief of severity of pruritus, a step-down approach with the NRS4 endpoint from
Week 2 to earlier time points was utilized as an additional family of hypothesis tests.
In general, for descriptive analyses, number and percent were presented for binary variables.
Number, mean, standard deviation, median, first and third quartiles were presented forcontinuous variables.
Estimates of the pairwise differences along with the two-sided 95% confidence interval (CI)were provided among the treatment groups, abrocitinib 200 mg QD, abrocitinib 100 mg QD,
dupilumab, and placebo.
RESULTS
Subject Disposition and Demography: A total of 1234 subjects were screened, and838 subjects were randomized. Similar proportions of subjects across the treatment groups
were ongoing in the study after completing 16 weeks. Subject discontinuations were low; themost common reasons for discontinuations were withdrawal by subjects (various reasons
including personal reasons and lack of efficacy) and AEs (Table S3).

Table S3. Disposition Events Summary
Placebo(N=131)

PF-04965842
100mg QD
(N=238)PF-04965842
200mg QD
(N=226)

Dupilumab 300mg
Q2W(N=242)

n (%)

n (%)

n (%)

n (%)

14 (10.7)

21 (8.8)

18 (8.0)

19 (7.9)5 (3.8)5 (2.1)8 (3.5)6 (2.5)Lack of Efficacy

01 (0.4)0

1 (0.4)

Lost to Follow-Up

1 (0.8)2 (0.8)1 (0.4)2 (0.8)

Number (%) of Subjects

Discontinued
Adverse Event

Pregnancy00

1 (0.4)1 (0.4)

Protocol Deviation

2 (1.5)2 (0.8)2 (0.9)1 (0.4)

Withdrawal By Subject

5 (3.8)9 (3.8)3 (1.3)6 (2.5)

Medication Error Without
Associated Adverse Event01 (0.4)1 (0.4)0

Other

1 (0.8)1 (0.4)2 (0.9)2 (0.8)Ongoing117(89.3)

217 (91.2)

208 (92.0)

223 (92.1)

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Table S3. Disposition Events Summary

Number (%) of Subjects

Placebo(N=131)

PF-04965842
100mg QD
(N=238)PF-04965842
200mg QD
(N=226)

Dupilumab 300mg
Q2W(N=242)

n (%)

n (%)

n (%)

n (%)

Disposition status was ongoing for subjects who did not discontinue from the study before Week 16.
Three subjects (13089008, 13469002, 12479010) had an AE that started before Week 16 and discontinued due to that AE
after Week 16. Those subjects were considered as ongoing in this table.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:17) Source Data: adds Output File:./nda1_cdisc/B7451029_CSR/adds_s001 Date of Generation: 07FEB2020 (07:56)
Table 14.1.1.2 is for Pfizer internal use.

Baseline demographic characteristics were balanced across treatment groups; the median age
was 34 years. Majority of the subjects were White (72.4%) and non-Hispanic or Latino(83.8%); 21.3% were of Asian descent and 4.2% were Black or African Americans.
Randomized subjects were representative of the moderate (64.6%) or severe (35.4%) AD
population at baseline per the IGA score; also, the median EASI was 27.2 and median BSA
involvement was 45.6%. The baseline PRO values were representative of a high burden of
disease and impact on quality of life (QoL). DLQI scores showed that subjects reported theirdisease had a "very large effect" on their QoL (median: 15.0). POEM scores indicatedsubjects reported their symptoms were "severe” (median: 22.0). Proportions of subjects who
had received prior systemic or topical treatment for AD were similar across treatment groups.
Efficacy Results:
Co-primary Endpoints: The study met both co-primary endpoints of IGA and EASI-75
responses at Week 12, demonstrating that both abrocitinib 200 mg and 100 mg treatmentgroups were superior to the placebo group. Also, responses with abrocitinib 200 mg dosewere higher than responses with abrocitinib 100 mg dose (Table S4, Table S5).
Additional supportive analyses for both co-primary endpoints were performed using the Per
Protocol Analysis Set (PPAS) population and using the Full Analysis Set (FAS) population
with a tipping point (TP) analysis where all missing responses were multiply imputed. For
both co-primary endpoints, the results of the PPAS and TP analyses were consistent with the
FAS primary analysis and conclusions remain unchanged.

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

N

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Dupilumab
300mg Q2W

129

235

219

241

n (%)

18 (14.0)

86 (36.6)

106 (48.4)

88 (36.5)

95% CI(8.0, 19.9)(30.4, 42.8)(41.8, 55.0)(30.4, 42.6)

23.1

34.8

22.5

(14.7, 31.4)(26.1, 43.5)(14.2, 30.9)<.0001<.0001

0.5

12.4(-8.0, 9.1)

(3.5, 21.3)

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]PF-04965842 - Dupilumab [1]Estimate (%)
95% CI
200 mg QD - 100 mg QD [1]Estimate (%)

12.1

95% CI(3.2, 21.1)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (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; IGA = investigator's global assessment; N = number ofsubjects in the analysis set with NRI at the specified visit; n (%) = number of subjects with response(percentage based onN); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of differenceby disease severity group using the normal approximation of binomial proportions. CI for the response rate was based on
normal approximation (or the Clopper-Pearson exact method when there were 0 or 100% responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:42) Source Data: adad Output File:./nda1_cdisc/B7451029_CSR/adad_s102_1 Date of Generation: 06FEB2020 (05:07)
Table 14.2.1.1.1.1 is for Pfizer internal use.

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Table S5. Proportion of Subjects Achieving EASI Response >= 75% Improvementfrom Baseline at Week 12 - CMH (FAS, NRI)
PlaceboN

PF-04965842 100mg
QD

PF-04965842 200mg
QD

Dupilumab 300mg Q2W

129

235

219

241

n (%)

35 (27.1)

138 (58.7)

154 (70.3)

140 (58.1)

95% CI(19.5, 34.8)(52.4, 65.0)(64.3, 76.4)(51.9, 64.3)

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

31.9

43.2

30.9

(22.2, 41.6)(33.7, 52.7)(21.2, 40.6)<.0001<.00010.8

12.0(-8.1, 9.6)

(3.3, 20.7)

PF-04965842 - Dupilumab[1]
Estimate (%)
95% CI
200 mg QD - 100 mg QD[1]
Estimate (%)
95% CI

11.5(2.8, 20.2)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (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; EASI = eczema area and severity index; N = number ofsubjects in the analysis set with NRI at the specified visit; n (%) = number of subjects with response (percentage based onN); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of differenceby disease severity group using the normal approximation of binomial proportions. CI for the response rate was based on
normal approximation (or the Clopper-Pearson exact method when there were 0 or 100% responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:43) Source Data: adea Output File:./nda1_cdisc/B7451029_CSR/adea_s104 Date of Generation: 06FEB2020 (02:53)
Table 14.2.1.1.3.1 is for Pfizer internal use.

Key Secondary Endpoints:
Both abrocitinib groups had statistically significant improvement compared with placeboin all 3 key secondary endpoints (p≤0.0002): proportion of subjects with PP-NRS4 at
Week 2, IGA response at Week 16, and EASI-75 at Week 16 (Table S6, Table S7,Table S8).

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CLINICAL STUDY REPORT SYNOPSISAt Week 2, abrocitinib 200 mg group compared with the dupilumab group, had
statistically significantly higher proportion of subjects with PP-NRS4, indicating earlier
onset of action (p<0.0001; Table S6).

At Week 16, abrocitinib 200 mg group compared with the dupilumab group, showed
higher proportion of IGA responders, based on 95% CI of the treatment difference
between the groups (Table S7).

At Week 16, proportion of EASI-75 responders was numerically greater in abrocitinib
200 mg group than in dupilumab group and was numerically lesser in abrocitinib 100 mg
group than in dupilumab group; 95% CI for the differences did not support true
difference in treatment responses (Table S8).

Table S6. Proportion of Subjects Achieving Pruritus NRS Severity Response >=4
Points Improvement from Baseline at Week 2 - CMH (FAS with Baseline>=4, NRI)

N

PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Dupilumab
300mg Q2W

130

236

226

239

n (%)

18 (13.8)

75 (31.8)

111 (49.1)

63 (26.4)

95% CI(7.9, 19.8)(25.8, 37.7)(42.6, 55.6)(20.8, 31.9)

17.9

34.9

12.5

(9.5, 26.3)(26.0, 43.7)(4.4, 20.7)

0.0002<.0001

5.2

22.1(-2.9, 13.4)(13.5, 30.7)

0.2084<.0001

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]PF-04965842 - Dupilumab [1]Estimate (%)
95% CI
Two-sided P-value [2]200 mg QD - 100 mg QD [1]Estimate (%)

17.2

95% CI(8.4, 26.0)

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Table S6. Proportion of Subjects Achieving Pruritus NRS Severity Response >=4
Points Improvement from Baseline at Week 2 - CMH (FAS with Baseline>=4, NRI)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Dupilumab
300mg Q2W

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (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; NRS= numeric rating scale.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of differenceby disease severity group using the normal approximation of binomial proportions. CI for the response rate was based on
normal approximation (or the Clopper-Pearson exact method when there were 0 or 100% responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:43) Source Data: adnr2 Output File:./nda1_cdisc/B7451029_CSR/adnr_s201_1 Date of Generation: 06FEB2020 (05:09)
Table 14.2.3.2.1 is for Pfizer internal use.

Table S7. Proportion of Subjects Achieving IGA Response of 'Clear' or 'Almost
Clear' and >=2 Points Improvement from Baseline at Week 16 - CMH(FAS, NRI)
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Dupilumab
300mg Q2W

124

230

221

232

n (%)

16 (12.9)80 (34.8)105 (47.5)

90 (38.8)

95% CI(7.0, 18.8)(28.6, 40.9)(40.9, 54.1)(32.5, 45.1)

22.1

35.0

25.6

(13.7, 30.5)(26.3, 43.7)(17.1, 34.1)<.0001<.0001-3.5

9.4(-12.2, 5.2)

(0.4, 18.5)

N

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]PF-04965842 - Dupilumab [1]Estimate (%)
95% CI
200 mg QD - 100 mg QD [1]Estimate (%)

13.1

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Table S7. Proportion of Subjects Achieving IGA Response of 'Clear' or 'Almost
Clear' and >=2 Points Improvement from Baseline at Week 16 - CMH(FAS, NRI)
PF-04965842
100mg QD

PlaceboPF-04965842
200mg QD

95% CI

Dupilumab
300mg Q2W

(4.2, 22.1)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (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; IGA = investigator's global assessment; N = number ofsubjects in the analysis set with NRI at the specified visit; n (%) = number of subjects with response(percentage based onN); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of differenceby disease severity group using the normal approximation of binomial proportions. CI for the response rate was based on
normal approximation (or the Clopper-Pearson exact method when there were 0 or 100% responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:42) Source Data: adad Output File:./nda1_cdisc/B7451029_CSR/adad_s102_3 Date of Generation: 06FEB2020 (05:05)
Table 14.2.1.2.1 is for Pfizer internal use.

Table S8. Proportion of Subjects Achieving EASI Response >= 75% Improvementfrom Baseline at Week 16 - CMH (FAS, NRI)
PlaceboPF-04965842 100mg
QD

PF-04965842 200mg
QD

Dupilumab 300mg Q2W

124

229

221

232

n (%)

38 (30.6)

138 (60.3)

157 (71.0)

152 (65.5)

95% CI(22.5, 38.8)(53.9, 66.6)(65.1, 77.0)(59.4, 71.6)

29.7

40.4

34.7

(19.5, 39.9)(30.4, 50.4)(24.6, 44.8)<.0001<.0001-5.1

5.5(-13.9, 3.7)(-3.1, 14.1)

N

Active - Placebo [1]Estimate (%)
95% CI
Two-sided P-value [2]PF-04965842 - Dupilumab[1]
Estimate (%)
95% CIPFIZER CONFIDENTIAL
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Table S8. Proportion of Subjects Achieving EASI Response >= 75% Improvementfrom Baseline at Week 16 - CMH (FAS, NRI)
PlaceboPF-04965842 100mg
QD

PF-04965842 200mg
QD

Dupilumab 300mg Q2W

200 mg QD - 100 mg QD[1]
Estimate (%)
95% CI

10.7(2.0, 19.4)

Full Analysis Set (FAS) was defined as all randomized subjects who received at least one dose of study medication.
Baseline was defined as the last measurement prior to first dosing (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; EASI = eczema area and severity index; N = number ofsubjects in the analysis set with NRI at the specified visit; n (%) = number of subjects with response (percentage based onN); NRI = non-responder imputation.
[1] The estimate and confidence interval (CI) for difference were calculated based on the weighted average of differenceby disease severity group using the normal approximation of binomial proportions. CI for the response rate was based on
normal approximation (or the Clopper-Pearson exact method when there were 0 or 100% responders).
[2] P-value was calculated using the Cochran-Mantel-Haenszel (CMH) method adjusted by baseline disease severity.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:43) Source Data: adea Output File:./nda1_cdisc/B7451029_CSR/adea_s104_1 Date of Generation: 06FEB2020 (02:55)
Table 14.2.2.1.1 is for Pfizer internal use.

Secondary Efficacy Endpoints: Additional secondary efficacy endpoints (IGA, EASI,PP-NRS, BSA, steroid-free days, and SCORAD) demonstrated improved efficacy in both
abrocitinib groups compared with the placebo group. The treatment effect of the abrocitinib
200 mg group was consistently higher than the abrocitinib 100 mg group. Abrocitinib
consistently had earlier onset of action than dupilumab and over time abrocitinib 200 mg
tended to be more effective than dupilumab.


IGA: At Weeks 2, 4, and 8 (also, at Week 12 [co-primary] and Week 16 [keysecondary]), both abrocitinib treatment groups showed statistically higher proportions ofsubjects with IGA responses compared with the placebo group (p≤0.0093). Bothabrocitinib groups had greater proportions of IGA responders than the dupilumab groupat Week 2, and the 200 mg group had more responders than dupilumab group at Weeks 4,
8, 12, and 16; these were true treatment differences per 95% CIs.



EASI-75: At Weeks 2, 4, and 8, (also, at Week 12 [co-primary] and Week 16 [keysecondary]) both abrocitinib treatment groups, compared with placebo group, showedstatistically significantly greater proportions of subjects with EASI-75 responses(p≤0.0006). Both abrocitinib treatment groups had greater proportions of EASI-75
responders than the dupilumab group at Week 2, and the 200 mg group had more
responders than dupilumab group at Weeks 4, 8, and 12; these were true treatment
differences per 95% CIs.
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EASI-50, EASI-90, EASI-100: Both abrocitinib treatment groups had statisticallysignificantly greater proportions of EASI-50 (p<0.0001) and EASI-90 (p≤0.0186)
responders compared with the placebo group at all time points. Statistically significantly
greater EASI-100 response was observed in abrocitinib 200 mg and 100 mg groups
compared with the placebo group as early as Week 2 (p=0.0142) and Week 8 (p=0.0041),
respectively; the statistically significant differences were maintained at each timepoint up
to Week 16 (p≤0.0095). Abrocitinib 200 mg group had greater proportion of EASI-100
responders than the dupilumab group at Weeks 2, 4, 8, 12, and 16; based on 95% CIs.



Total EASI, change from baseline: The least squares mean (LSM) of percent change
from baseline in the total EASI score demonstrated statistically significant improvement
in both abrocitinib treatment groups compared with the placebo group at all scheduled
time points (p<0.0001). Both abrocitinib treatment groups had greater improvement thanthe dupilumab group at Week 2, and the 200 mg group maintained the improvement overdupilumab at Weeks 4, 8, and 12; these were true treatment differences per 95% CIs.



PP-NRS4: As early as Day 4 and Day 9, abrocitinib 200 mg (p=0.0023) and 100 mg(p=0.0202) groups, respectively, had statistically significantly higher proportions of
PP-NRS4 responders compared with the placebo group; the statistical significance wasmaintained at all timepoints up to Week 16 (p≤0.0106). As compared with the
dupilumab group, abrocitinib 200 mg group had statistically significantly greater
proportions of PP-NRS4 responders as early as Day 4 (p<0.0001) and at all timepoints up
to Day 15 (p≤0.0049); also, at all subsequent timepoints up to Week 8 (based on 95%
CI).

Time to PP-NRS4: The Kaplan-Meier analysis to estimate the time to first PP-NRS4
showed the time to response was statistically significantly faster in both abrocitinib
groups compared with the placebo group with 50% achieving a PP-NRS4 response in
200 mg and 100 mg groups by 13 and 29 days, respectively. Also, the response was
faster in abrocitinib 200 mg group than in the dupilumab group; median time to achieve
first PP-NRS4 response in abrocitinib 200 mg group and dupilumab group was 13 daysand 31 days, respectively; the 95% CIs supported a true difference in treatment response.

PP-NRS, change from baseline: As early as Day 2, the LSM of percent change frombaseline in PP-NRS was improved in both abrocitinib groups compared with the placebogroup (p≤0.0331), demonstrating a rapid onset of the treatment effect, which wasmaintained at all timepoints (p≤0.0200). At Day 2, both abrocitinib treatment groups hadgreater improvement in LSM of percent change from baseline in PP-NRS than the
dupilumab group, which was maintained in the 200 mg group at all timepoints up to
Week 12; based on 95% CIs.



SCORAD50 and SCORAD75: Both abrocitinib treatment groups demonstrated
statistically significantly higher proportions of subjects with SCORAD50 and
SCORAD75 responses compared with the placebo group as early as Week 2 (p≤0.034);
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maintained at all timepoints up to Week 16 (p≤0.0026). Proportion of SCORAD50
responders was higher in abrocitinib 200 mg group than in dupilumab group at Weeks 2,
4, and 8; proportion of SCORAD75 responders was higher in abrocitinib 200 mg groupthan in dupilumab group at Weeks 2, 4, 8, 12, and 16 (supported by 95% CIs).


SCORAD total score, change from baseline: Based on the mixed effect repeatedmeasures (MMRM) analysis, both abrocitinib treatment groups demonstrated statisticallysignificantly greater decreases compared with the placebo group in absolute and percent
change from baseline of SCORAD total score, beginning at Week 2 that were maintained
up to Week 16 (p<0.0001). The decreases in abrocitinib 200 mg group were greater thanthose in dupilumab group, at Weeks 2, 4, 8, and 12, based on 95% CIs.



SCORAD visual analog scale (VAS), change from baseline: Both abrocitinib treatmentgroups demonstrated statistically significant decreases (improvement) compared with theplacebo group in LSM of change from baseline in SCORAD VAS of sleep loss at
Weeks 2, 4, 8, 12, and 16 (p≤0.0002 for absolute change and p≤0.0008 for percent
change). Abrocitinib 200 mg group showed greater decrease than dupilumab group in
LSM of absolute change from baseline in SCORAD VAS of sleep loss at Weeks 2, 4, 8,
and 16; based on 95% CIs.



Percent BSA, change from baseline: Based on the MMRM analysis, both abrocitinib
groups demonstrated statistically significant decreases from baseline in %BSA (absolutechange and percent change) compared with the placebo group as early as Week 2,maintained at Weeks 4, 8, 12, and 16 (p<0.0001). At Week 2, abrocitinib 200 mg group
showed greater decreases from baseline in %BSA (absolute and percent change) than in
the dupilumab group; the decreases in absolute change were maintained at Weeks 4, 8,
12, and 16 and decreases in percent change were maintained at Week 4 and Week 8;
supported by 95% CIs .



Steroid-free days: LSM of number of days up to Week 16 when corticosteroid was not
used was statistically significantly higher in the abrocitinib 200 mg group compared withthe placebo group (p=0.0082).

Patient-Reported Outcomes
PtGA: The LSM of change from baseline in PtGA scores was statistically significantly
improved (lower) in both abrocitinib treatment groups compared with the placebo groupbeginning at Week 2 that were maintained up to Week 16 (p≤0.0002). Abrocitinib 200 mg
group showed more improved LSM of change from baseline in PtGA scores than the
dupilumab group at Weeks 2, 4, 8, and 12; based on 95% CIs.
DLQI: The LSM of change from baseline in DLQI scores was statistically significantly
improved (lower than baseline) in both abrocitinib treatment groups compared with theplacebo group at Weeks 2, 12, and 16 (p≤0.0003). Abrocitinib 200 mg group showed more
improved LSM of change from baseline in DLQI scores than the dupilumab group at
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Weeks 2, 12, and 16; based on 95% CIs. Also, there were statistically significantly greater
proportion of DLQI responders (≥4 points improvement from baseline) in both abrocitinib
groups than in placebo group.
EQ-5D-5L: The LSM of change from baseline was statistically improved (higher) for both
abrocitinib treatment groups compared with the placebo group at Week 12 (p<0.0001) andWeek 16 (p≤0.0342). The LSM of change from baseline was more improved in abrocitinib
200 mg group than in dupilumab group at Week 12; based on 95% CIs. The analyses fordata on EQ VAS scores showed improvement in abrocitinib 200 mg group compared withthe placebo group at Week 12 (p<0.0001) and Week 16 (p<0.0001).
HADS: The LSMs of change from baseline in HADS anxiety and depression subscales were
statistically significantly improved (lower) for both abrocitinib treatment groups comparedwith the placebo group at Week 12 and Week 16 (p≤0.0222).
POEM: The LSM of change from baseline in POEM scores was statistically significantly
improved (lower) for both abrocitinib treatment groups compared with the placebo group at
Week 12 and Week 16 (p<0.0001). The LSM of change from baseline in POEM scores wasmore improved in abrocitinib 200 mg group than in dupilumab group at Week 12 andWeek 16; based on 95% CIs.
PSAAD: As early as Week 1, both abrocitinib treatment groups showed statisticallysignificant improvement (lower than baseline) compared with placebo group in LSM ofchange from baseline in PSAAD scores; the improvement was maintained at each weekly
timepoint up to Week 16 (p≤0.0001). The LSM of change from baseline in PSAAD scores
was more improved in abrocitinib 200 mg group than in dupilumab group starting at Week 1
and at each weekly timepoint up to Week 10; based on 95% CIs
Safety Results:The proportion of subjects with all-causality TEAEs was higher for the abrocitinib 200
mg group compared to the abrocitinib 100 mg, dupilumab and placebo groups (Table S9).
o The majority of all-causality TEAEs were mild or moderate.
o The incidence of subjects reporting severe all-causality TEAEs was low and similar
between all treatment groups.
o The highest incidence of treatment-related TEAEs occurred in the abrocitinib 200 mg
group (approximately 30%), with similar incidence in the abrocitinib 100 mg,
dupilumab and placebo groups (approximately 20%).



Serious TEAEs were reported in similar proportion of subjects across the treatmentgroups. No deaths were reported in the study (Table S9).

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Discontinuations from the study due to TEAEs were low and similar across the treatmentgroups (Table S9).

Table S9. Treatment-Emergent Adverse Events (All Causalities) - Safety Analysis
Set
PlaceboPF-04965842
100mg QD

PF-04965842
200mg QD

Dupilumab 300mg
Q2W

Number (%) of Subjects

n (%)

n (%)

n (%)

n (%)

Subjects evaluable for adverse events

131

238

226

242

Number of adverse events

150

269

308

223

Subjects with adverse events

70 (53.4)

121 (50.8)

140 (61.9)

121 (50.0)

Subjects with serious adverse events

5 (3.8)6 (2.5)2 (0.9)2 (0.8)

Subjects with severe adverse events

3 (2.3)5 (2.1)4 (1.8)2 (0.8)

Subjects discontinued from study due toadverse events [1]5 (3.8)6 (2.5)

10 (4.4)

8 (3.3)

Subjects discontinued study drug due to AE
and continued Study [2]2 (1.5)2 (0.8)1 (0.4)0Subjects with temporary discontinuation
due to adverse events

9 (6.9)15 (6.3)

12 (5.3)9 (3.7)

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. Threesubjects (13089008, 13469002, 12479010) had an AE that started before Week 16 and discontinued due to that AE after
Week 16. Those AEs were also included in this table.
[2] Subjects who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did
not cause the subject to be discontinued from study
MedDRA v22.1 coding dictionary applied.
PFIZER CONFIDENTIAL SDTM Creation: 01FEB2020 (21:40) Source Data: adae Output File:./nda1_cdisc/B7451029_CSR/adae_s010 Date of Generation: 07FEB2020 (07:53)
Table 14.3.1.2.1 is for Pfizer internal use.

Conclusion(s):EFFICACY
Co-Primary Endpoints:

The study met both co-primary endpoints of IGA and EASI-75 responses at Week 12,
demonstrating that both abrocitinib 200 mg and 100 mg treatment groups were superior
to the placebo group.
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o IGA responses and EASI-75 responses in the abrocitinib 200 mg group were higher
than the abrocitinib 100 mg 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:
Both abrocitinib groups had statistically significant improvement compared with placeboin all 3 key secondary endpoints (p≤0.0002): proportion of subjects with PP-NRS4 at
Week 2, IGA response at Week 16, and EASI-75 at Week 16.



At Week 2, abrocitinib 200 mg group compared with the dupilumab group, had
statistically significantly higher proportion of subjects with PP-NRS4, indicating earlier
onset of action (p<0.0001).



At Week 16, abrocitinib 200 mg group compared with the dupilumab group, showed
higher proportion of IGA responders, based on 95% CI of the treatment difference
between the groups.



At Week 16, proportion of EASI-75 responders was numerically greater in abrocitinib
200 mg group than in dupilumab group and was numerically lesser in abrocitinib 100 mg
group than in dupilumab group; 95% CI for the differences did not support true
difference in treatment responses.

Other Secondary Endpoints:
Additional secondary efficacy endpoints (IGA, EASI, PP-NRS, BSA, SCORAD, and steroidfree days) demonstrated improved efficacy in both abrocitinib groups compared with theplacebo group. The treatment effect of the abrocitinib 200 mg group was consistently higher
than the abrocitinib 100 mg group.
Also, abrocitinib consistently had earlier onset of action than dupilumab. Over time
abrocitinib 200 mg tended to be more effective than dupilumab, while abrocitinib 100 mg
tended to be comparable to dupilumab.
IGA Responses (Clear (0) or Almost Clear (1) and 2 Point Reduction from Baseline)Both abrocitinib treatment groups had statistically significantly greater proportion of IGA
responders compared with placebo at all time points.

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Both abrocitinib groups had greater proportions of IGA responders than the dupilumab
group at Week 2, and the 200 mg group had more responders than dupilumab group at
Weeks 4, 8, 12, and 16; these were true treatment differences per 95% CIs.

EASIBoth abrocitinib treatment groups had statistically significantly greater proportions of
EASI-50, EASI-75 and EASI-90 responders compared with the placebo group at all time
points. Statistically significantly greater EASI-100 response was observed in abrocitinib
200 mg and 100 mg groups compared with the placebo group as early as Week 2 andWeek 8, respectively; the statistically significant differences were maintained at eachtime point up to Week 16.

Both abrocitinib treatment groups compared with the placebo group demonstrated
statistically significant improvement from baseline in the total EASI score at each
timepoint up to Week 16.

Both abrocitinib group had earlier onset of action than dupilumab group based on
observations in change from baseline in the total EASI score and responders for EASI-50,
EASI-75, EASI 90, and EASI 100; the greater than dupilumab responses were maintained
for longer duration in the abrocitinib 200 mg group.

PP-NRS for SeverityAs early as Day 2, the LSM of percent change from baseline in PP-NRS was lower inboth abrocitinib groups compared with the placebo group, demonstrating a rapid onset of
the treatment effect, which was maintained at each timepoint up to Week 16.

The median time to achieve first PP-NRS4 was faster in both abrocitinib treatmentgroups compared with the placebo group.

Both abrocitinib groups had earlier onset of action than the dupilumab group; mediantime to PP-NRS4 was 31 days in the dupilumab group. The greater difference in PP-NRS
effect was maintained longer in abrocitinib 200 mg group.

SCORAD

Both abrocitinib treatment groups compared with the placebo demonstrated statisticallysignificantly greater decreases in SCORAD total score and SCOARD VAS for sleep loss
as early as Week 2 and maintained at each timepoint up to Week 16.

Both abrocitinib treatment groups demonstrated statistically significantly greater
SCORAD75 and SCORAD50 responses compared with the placebo group beginning at
Week 2 and maintained at each timepoint up to Week 16.

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CLINICAL STUDY REPORT SYNOPSISAt Week 2, both abrocitinib groups demonstrated greater decrease than dupilumab groupin SCORAD total score, greater proportions of SCORAD50 and SCORAD75 responders,and greater decrease from baseline in SCORAD VAS for sleep loss; the effects weremaintained longer in abrocitinib 200 mg group.

BSA

Both abrocitinib treatment groups compared with placebo demonstrated statisticallysignificant decreases in %BSA as early as Week 2 and maintained at each timepoint up to
Week 16.



At Week 2, abrocitinib 200 mg group demonstrated greater decreases in %BSA than in
the dupilumab group.

Steroid-free days:


Number of days up to Week 16 when corticosteroid was not used was statisticallysignificantly lower in the abrocitinib 200 mg group compared with the placebo group.

Patient-Reported Outcomes (PROs):
Favorable and improved differences across all PRO measures were observed for both
abrocitinib treatment groups compared with the placebo group. Treatment differences
emerged as early as Week 2 and were maintained at subsequent time points up to Week 16.
Abrocitinib 200 mg group tended to demonstrate more treatment effect than the abrocitinib
100 mg group. Abrocitinib groups generally had earlier onset than dupilumab group.


PtGA: Scores were statistically significantly improved in both abrocitinib groups
compared with the placebo group from Week 2 to Week 16; and the abrocitinib 200 mg
group showed more improvement than the dupilumab group from Week 2 to Week 12.



DLQI: Scores were statistically significantly improved in both abrocitinib groups
compared with the placebo group at Weeks 2, 12, and 16; the 200 mg group showed more
improvement than the dupilumab group at Weeks 2, 12, and 16. Also, there were
statistically significantly greater proportions of responders (≥4 points improvement frombaseline) in both abrocitinib groups than in placebo group.



EQ-5D-5L: Index value was statistically significantly improved for both abrocitinib
groups compared with the placebo group at Weeks 12 and 16, and more improved in
200 mg group than dupilumab group at Week 12. The VAS score was improved forabrocitinib 200 mg group compared with the placebo group at Weeks 12 and 16.



HADS: Both abrocitinib groups compared with the placebo group had statisticallysignificant improvement in symptoms associated with depression and anxiety at Weeks
12 and 16.
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POEM: Scores were statistically significantly improved in both abrocitinib groups
compared with the placebo group at Weeks 12, and 16; and the 200 mg group showed
more improvement than the dupilumab group at both timepoints.



PSAAD: As early as Week 1, the scores were statistically significantly improved in both
abrocitinib groups compared with the placebo group, and improvement was maintained ateach weekly timepoint up to Week 16; the 200 mg group showed more improvement thanthe dupilumab group at Week 1 and maintained it at each weekly timepoint up to
Week 10.

SAFETY

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

A higher proportion of subjects with all-causality TEAEs occurred in the abrocitinib 200
mg group compared with the abrocitinib 100 mg, dupilumab and placebo groups.
All-causality TEAEs that appeared more commonly in the abrocitinib groups relative
to the dupilumab or placebo groups included nausea, headache, nasopharyngitis, upper
respiratory tract infection, herpes simplex, blood creatine phosphokinase increased andacne. A higher incidence of conjunctivitis was observed in the dupilumab groupcompared to either abrocitinib group or placebo.

The incidence of TEAEs related to atopic dermatitis was more frequent in the placebogroup compared with either abrocitinib group and the dupilumab group.

The majority of all-causality TEAEs were mild or moderate in severity.



The incidence of severe all-causality TEAEs was low and similar between alltreatment groups.



No deaths were reported in the study.



The incidence of SAEs was low and similar across the treatment groups.

Discontinuations from the study due to TEAEs were low and similar across the treatmentgroups.



The incidence of herpes zoster was low, one subject (1/238 [0.4%]) in the abrocitinib 100
mg QD group had a severe TEAE, and no subjects in the abrocitinib 200 mg group,
dupilumab group or placebo group had a severe TEAE.



Platelet counts decreased in a dose-dependent manner in both abrocitinib groups with anadir at Week 4 and returned toward baseline through Week 16 despite continued
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abrocitinib administration in the majority of subjects. No changes from baseline wereobserved for the dupilumab group. No subjects met pre-specified monitoring criteria, andno subject met pre-specified discontinuation criteria. Median lymphocyte counts,
neutrophil counts, and hemoglobin values showed no clinically meaningful medianchanges.


There were increases in both abrocitinib groups for total cholesterol, low density
lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol, where
dose-dependent changes were observed for total cholesterol, HDL-cholesterol andtriglycerides. There were no changes over time in LDL/HDL ratio. No meaningfulchanges were observed in the dupilumab group.



Dose-dependent increases in creatine kinase were observed in the abrocitinib groups
compared with the placebo group but were not clinically meaningful. No medianchanges from baseline creatine kinase values were observed for the dupilumab group.
There were no TEAEs of rhabdomyolysis.

Two (2) adjudicated malignancy events (abrocitinib 200 mg group and dupilumab group)
occurred in the study. One subject had actinic keratosis (abrocitinib 200 mg group) per
histopathology review. None of the subjects had any findings from cardiovascularreview or opportunistic infections review.



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

PFIZER CONFIDENTIAL
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