101102042_Cobi_Pop_PK_L1a Presented at the Winter Clinical Dermatology Conference; January 13-18, 2023; Kohala Coast, Hawaii Copies of this poster obtained through this QR code, are for your personal use only and may not be reproduced without permission from the authors. Copyright © 2023. All rights reserved. BACKGROUND • Dupilumab, an anti–interleukin 4 receptor alpha monoclonal antibody, is approved for the treatment of patients with atopic dermatitis (AD) who are candidates for systemic therapy1 • Patients with moderate-to-severe AD who do not respond to dupilumab have limited treatment options • Abrocitinib is a Janus kinase 1 (JAK1) inhibitor that is under investigation for the treatment of moderate-to-severe AD2,3 OBJECTIVE • To assess the proportion of dupilumab nonresponder patients from JADE COMPARE who experienced clinically meaningful improvement in signs and symptoms of AD after switching to abrocitinib in JADE EXTEND METHODS • Phase 3 JADE COMPARE included adults with moderate-to-severe AD and inadequate response to topical medication or a need for systemic therapy to control AD • This post hoc analysis focused on patients with moderate-to-severe AD who received dupilumab and concomitant topical therapy for 16 weeks in JADE COMPARE followed by entry into JADE EXTEND (Figure 1) • Upon entering JADE EXTEND, patients were randomized to either abrocitinib 200 mg or 100 mg once daily • In JADE EXTEND, medicated topical therapy was permitted but not required • Patients who did not achieve an Investigator’s Global Assessment (IGA) of 0 or 1 with ≥2-point improvement, ≥75% or ≥90% improvement in Eczema Area and Severity Index (EASI), 4-point improvement on the Peak Pruritus Numerical Rating Scale (PP-NRS), or PP-NRS score of 0 or 1 at week 16 with dupilumab were reassessed at week 32 with abrocitinib 200 mg or 100 mg • Safety was assessed by monitoring treatment-emergent adverse events (TEAEs) Figure 1. Study Design Medicated topical therapy (low- and/or medium-potency corticosteroids, calcineurin inhibitors, and phosphodiesterase 4 inhibitor) required for active lesions Medicated topical therapy was permitted but not required Dupilumab 300 mg SC Q2W + Oral Placebo QD (n=242) Oral Placebo Abrocitinib 100 mg QD (n=130) Abrocitinib 200 mg QD (n=73) Treatment period: 16 weeks (last dupilumab dose at week 14) 4-week washout Current analysis Week 32 Week 20 Week 16 Week 0Eligibility Criteria • Adult patients (≥18 years) with AD ≥1 year • Moderate-to-severe AD (IGA ≥3; EASI ≥16; %BSA ≥10; PP-NRS ≥4) • Inadequate response to topical medication, or need for systemic therapy to control AD JADE COMPARE JADE COMPARE JADE EXTEND AD, atopic dermatitis; %BSA, percentage of affected body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; PP-NRS, Peak Pruritus Numerical Rating Scale; Q2W, every 2 weeks; QD, once daily; SC, subcutaneous. The PP-NRS is used with permission of Regeneron Pharmaceuticals, Inc., and Sanofi. RESULTS Patients • Disease characteristics were well balanced across treatment arms at entry to JADE EXTEND (Table 1) • Most patients had moderate AD per IGA: 64.4% of patients in the 200-mg arm and 66.9% in the 100-mg arm Abrocitinib in the Treatment of Moderate-to-Severe Atopic Dermatitis Refractory to Dupilumab Treatment: An Analysis of JADE-EXTEND, a Phase 3 Long-Term Extension Study Vivian Shi,1 Tina Bhutani,2 Mette Deleuran,3 Luz Fonacier,4 Stephen Shumack,5 Fan Zhang,6 Michael C. Cameron,7 Gary Chan,6 Hernan Valdez,7 Natalie Yin7 1University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2UCSF, San Francisco, CA, USA; 3Aarhus University Hospital, Aarhus, Denmark; 4NYU Langone Hospital–Long Island, New York, NY, USA; 5University of Sydney, Royal North Shore Hospital, Sydney, NSW, Australia; 6Pfizer Inc., Groton, CT, USA; 7Pfizer Inc., New York, NY, USA Table 1. Baseline Characteristics (Safety Population)a Abrocitinib 100 mg QD n=130 Abrocitinib 200 mg QD n=73 Duration of AD, mean (SD), y 24.2 (15.0) 23.6 (15.6) IGA, n (%) Moderate (3) Severe (4) 87 (66.9) 43 (33.1) 47 (64.4) 26 (35.6) %BSA, mean (SD) 45.4 (21.2) 47.9 (22.9) EASI, mean (SD) 29.6 (11.2) 31.2 (12.4) PP-NRS, mean (SD) 7.4 (1.7) 7.2 (1.6) AD, atopic dermatitis; %BSA, percentage of affected body surface area; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; PP-NRS, Peak Pruritus Numerical Rating Scale; QD, once daily; SD, standard deviation. aSafety population represents all patients who received prior dupilumab in JADE COMPARE and were randomly assigned to receive abrocitinib in JADE EXTEND. Efficacy • A substantial portion of dupilumab nonresponders achieved clinically meaningful efficacy responses after switching to abrocitinib (Figure 2) • Among dupilumab IGA 0/1 nonresponders (based on failing to achieve an IGA of clear [0] or almost clear [1] and ≥2-grade improvement from baseline in JADE COMPARE), 47.2% of the abrocitinib 200-mg group and 35.2% of the abrocitinib 100-mg group achieved IGA 0/1 at week 12 of JADE EXTEND • Among dupilumab EASI-75 nonresponders (based on failing to achieve at least a 75% improvement from baseline in EASI in JADE COMPARE), 80.0% of the abrocitinib 200-mg group and 67.7% of the abrocitinib 100-mg group achieved EASI-75 at week 12 of JADE EXTEND • Among dupilumab EASI-90 nonresponders (based on failing to achieve at least a 90% improvement from baseline in EASI in JADE COMPARE), 59.5% of the abrocitinib 200-mg group and 39.7% of the abrocitinib 100-mg group achieved EASI-90 at week 12 of JADE EXTEND • Among dupilumab PP-NRS4 nonresponders (based on failing to achieve at least a 4-point improvement from baseline in PP-NRS in JADE COMPARE), 77.3% of the abrocitinib 200-mg group and 37.8% of the abrocitinib 100-mg group achieved PP-NRS4 at week 12 of JADE EXTEND (representing a clinically meaningful improvement in itch) • Among dupilumab PP-NRS 0/1 nonresponders (based on failing to achieve a PP-NRS score of 0 [representing no itch] or 1 [representing minimal itch] in JADE COMPARE), 42.9% of the abrocitinib 200-mg group and 25.8% of the abrocitinib 100-mg group achieved PP-NRS 0/1 at week 12 of JADE EXTEND Figure 2. Abrocitinib Efficacy at Week 12 Among Dupilumab Nonresponders 60 70 80 90 100 0 10 20 30 40 50 P ro po rt io n of P at ie nt s, % na IGA 0/1 71 36 35.2 47.2 EASI-75 31 20 67.7 80.0 EASI-90 68 37 39.7 59.5 PP-NRS4 45 22 37.8 77.3 PP-NRS 0/1 89 42 25.8 42.9 Abrocitinib 100 mg QD Abrocitinib 200 mg QD EASI-75, ≥75% improvement from baseline in Eczema Area and Severity Index; EASI-90, ≥90% improvement from baseline in Eczema Area and Severity Index; IGA 0/1, Investigator’s Global Assessment of clear (0) or almost clear (1) and ≥2-grade improvement from baseline; PP-NRS4, ≥4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score; PP-NRS 0/1, Peak Pruritus Numerical Rating Scale score of 0 (no itch) or 1 (minimal itch); QD, once daily. aNumber of dupilumab nonresponders according to each efficacy endpoint at week 16 of JADE COMPARE. Safety • TEAEs were reported in 50.7% of patients in the abrocitinib 200-mg group and in 41.5% of patients in the abrocitinib 100-mg group (Table 2) • The incidence of adverse events (AEs) that were serious, severe, or led to study discontinuation was <3% • The most common AE in both abrocitinib treatment arms was nasopharyngitis, occurring in 11.0% of patients in the 200-mg group and 6.9% of patients in the 100-mg group Table 2. Safety Abrocitinib 100 mg QD n=130 Abrocitinib 200 mg QD n=73 Patients who had ≥1 TEAE, n (%) Serious Severe Leading to study discontinuation 54 (41.5) 3 (2.3) 3 (2.3) 1 (0.8) 37 (50.7) 1 (1.4) 2 (2.7) 1 (1.4) TEAEs reported for ≥4 patients in any group, n (%) Nasopharyngitis Nausea Acne Headache Upper respiratory tract infection Urinary tract infection 9 (6.9) 0 3 (2.3) 1 (0.8) 6 (4.6) 4 (3.1) 8 (11.0) 6 (8.2) 5 (6.8) 5 (6.8) 2 (2.7) 1 (1.4) QD, once daily; TEAE, treatment-emergent adverse event. CONCLUSIONS • In a substantial proportion of dupilumab nonresponders, clinically meaningful improvement in signs (IGA, EASI-75, EASI-90) and symptoms (PP-NRS4, PP-NRS 0/1) of moderate-to-severe AD was achieved after switching to abrocitinib • The safety profile of abrocitinib in JADE EXTEND was consistent with previous studies; no new safety signals were observed at 12 weeks • The efficacy and safety profile of oral abrocitinib 200 mg or 100 mg QD in this analysis supports the role of abrocitinib as treatment for patients with moderate-to-severe AD, regardless of prior experience with dupilumab REFERENCES 1. Dupixent (dupilumab) injection, for subcutaneous use (prescribing information). Bridgewater, NJ: Sanofi and Regeneron Pharmaceuticals; May 2020. 2. Simpson EL et al. Lancet. 2020;396:255-266. 3. Silverberg JI et al. JAMA Dermatol. 2020;156:863-873. ACKNOWLEDGMENTS Editorial/medical writing support under the guidance of authors was provided by Renee Gordon, PhD, and Richard W. Davis IV, PhD, at ApotheCom (San Francisco, CA, USA), and was funded by Pfizer Inc., New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med. 2022; 10.7326/M22-1460). These studies were sponsored by Pfizer, Inc. Previously presented at the American Academy of Dermatology VMX 2021 Congress [Virtual]; April 23-25, 2021. DISCLOSURES VS is a stock shareholder of Learn Health and has served as an advisory board member or investigator and/or received research funding from Pfizer Inc., Sanofi-Genzyme, Regeneron, AbbVie, Eli Lilly, Novartis, SUN Pharma, LEO Pharma, Menlo Therapeutics, Dermira, Burt’s Bees, Galderma, Kiniksa Pharmaceuticals, UCB, Altus Lab, MYOR, Polyfin, GpSkin, and Skin Actives Scientific. TB is an investigator for Pfizer Inc., AbbVie, Galderma, Mindera, and Regeneron. She has served as a consultant and/or advisory board member for Pfizer Inc., AbbVie, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO Pharma, Lilly, Novartis, Sun, and UCB. MD has been a consultant, advisory board member, and/or speaker for Pfizer Inc., AbbVie, Eli Lilly, LEO Pharma, Regeneron, Sanofi-Genzyme, and Pierre Fabre. LF has been a consultant and advisory board member for Pfizer Inc., Regeneron, AbbVie, and Lilly, and has received research and educational grants (made to NYU Langone Hospital–Long Island) from Pfizer Inc., Regeneron, AstraZeneca, and Shire. SS has been an investigator, advisory board member, and/or speaker for Pfizer Inc., AbbVie, Lilly, LEO Pharma, Sanofi, and Novartis. MCC is a former employee of Pfizer Inc. and may hold stock options. FZ, GC, HV, and NY are employees and shareholders of Pfizer Inc.