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 • The long-term, relapsing-remitting nature of atopic dermatitis (AD) often requires flexibility in treatment, such as dose reduction and treatment interruption1 • The JADE REGIMEN trial (NCT03627767), which included patients with moderate-to-severe AD, was conducted to evaluate maintenance of response to the Janus kinase 1 (JAK) inhibitor abrocitinib with continuous dosing, reduced dose, or withdrawal of abrocitinib2 – Patients who stopped responding (experienced flare) during the maintenance period received rescue treatment OBJECTIVE • To evaluate the efficacy and safety of rescue therapy in JADE REGIMEN METHODS Patients • JADE REGIMEN was a multicenter, double-blind, responder-enriched, placebo-controlled, phase 3, randomized-withdrawal study (Figure 1) – The induction period consisted of 12 weeks of treatment with abrocitinib 200 mg by mouth once daily – Patients who responded to induction (achieved Investigator’s Global Assessment [IGA] score of 0/1 with ≥2-point reduction from baseline and ≥75% improvement in Eczema Area and Severity Index [EASI] response) were randomly assigned to dose continuation, dose reduction, or withdrawal of abrocitinib for 40 weeks (maintenance period) – Patients who experienced flare during the maintenance period (ie, lost ≥50% of week 12 EASI response and had a new IGA score ≥2) received rescue therapy (abrocitinib 200 mg + topical medicated treatment) for 12 weeks Figure 1. JADE REGIMEN Study Design Randomization of Respondersc 1:1:1 N=798 End of Treatment End of Study Open-Label Induction Period 40-Week Maintenance Treatment Period Follow-Up Period Day 1 Week 52 Week +4Week 12 Screening: 28 days Medicated topical washout period: 3 days Placebo QD (n=267) Abrocitinib 200 mg QD (n=266) Abrocitinib 100 mg QD (n=265)Abrocitinib 200 mg QDN=1233 12-Week Rescue Treatment Period for Patients Experiencing Flarea Abrocitinib 200 mg QD + Topical Therapyb QD, once daily. aFlare was defined as ≥50% loss of EASI response at randomization and IGA score ≥2. b Topical therapy was permitted only during the rescue period and included topical corticosteroids, calcineurin inhibitors (tacrolimus or pimecrolimus), and phosphodiesterase 4 inhibitors (crisaborole) when required per local standard of care. cResponder criteria at week 12 are defined as IGA score 0/1 with ≥2-point reduction from baseline and ≥75% improvement from baseline in EASI response. Patients • Eligible patients were aged ≥12 years, had moderate-to-severe AD (IGA score ≥3; EASI score ≥16; percentage of body surface area [%BSA] affected ≥10; Peak Pruritus Numerical Rating Scale [PP-NRS; used with permission from Regeneron Pharmaceuticals Inc. and Sanofi score ≥4) for ≥1 year, and had inadequate response or intolerance to topical medication or required systemic therapy to control AD Analysis • Recaptured IGA, EASI, and PP-NRS responses, defined as scores not worse than responses at randomization baseline in patients who received rescue therapy, were assessed at all scheduled time points during the rescue period • Safety was assessed through adverse events (AEs) RESULTS Efficacy • In the abrocitinib 200-mg, abrocitinib 100-mg, and placebo arms, 43 (16.2%), 104 (39.2%), and 204 (76.4%) patients, respectively, entered the rescue period after experiencing protocol-defined flare • By week 12 of the rescue period, 74%, 57%, and 68% patients who had been randomly assigned to undergo withdrawal of abrocitinib (ie, placebo) were able to recapture their IGA, EASI, and PP-NRS responses, respectively (Figures 2A-C) • Among patients who were randomly assigned to receive abrocitinib 200 mg, recapture rates were 36% (IGA), 33% (EASI), and 29% (PP-NRS); the corresponding rates among those who had received abrocitinib 100 mg were 51%, 32%, and 40%, respectively (Figures 2A-C) Figure 2. Proportions of Patients Who Recaptured (A) IGA, (B) EASI, and (C) PP-NRS Responsesa With Rescue Therapy After Experiencing Protocol-Defined Flareb 100 0 2 4 8 120 20 40 60 80 51.4 68.2 71.6 68.2 31.9 40.9 41.2 39.7 38.7 41.4 27.6 28.6 C P at ie nt s, % (9 5% C I) Time, weeks Evaluable patients, n Placebo Abrocitinib 100 mg QD Abrocitinib 200 mg QD 157 88 29 169 85 29 173 94 31 88 58 21 Abrocitinib 200 mg � Placebo Abrocitinib 200 mg � Abrocitinib 100 mg Abrocitinib 200 mg � Abrocitinib 200 mg 100 0 2 4 8 120 20 40 60 80 19.8 44.9 50.7 57.1 8.0 25.0 30.7 32.0 7.3 17.5 22.0 33.3 B P at ie nt s, % (9 5% C I) Time, weeks Evaluable patients, n Placebo Abrocitinib 100 mg QD Abrocitinib 200 mg QD 198 100 40 203 101 41 192 100 41 196 103 42 100 0 2 4 8 120 20 40 60 80 26.0 58.1 67.0 74.0 20.0 42.0 45.5 50.5 17.1 22.5 31.7 35.7 A P at ie nt s, % (9 5% C I) Time, weeks Evaluable patients, n Placebo Abrocitinib 100 mg QD Abrocitinib 200 mg QD 198 100 40 203 101 41 192 100 41 196 103 42 EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; PP-NRS, Peak Pruritus Numerical Rating Scale; QD, once daily. ªRecapture of response was defined as a score not worse than the score at randomization baseline. bFlare was defined as ≥50% loss of week 12 EASI response and IGA score ≥2. Safety • AEs were experienced by a greater proportion of patients who entered the rescue period from the abrocitinib 200-mg treatment arm (55.8%) than from the placebo arm (33.8%) or the abrocitinib 100-mg arm (30.8%) (Table 1) – Most AEs in the rescue period were mild or moderate across treatment arms Table 1. Summary of Adverse Events During the Rescue Period of JADE REGIMEN Abrocitinib 200 mg  Placebo n=204 Abrocitinib 200 mg  Abrocitinib 100 mg n=104 Abrocitinib 200 mg  Abrocitinib 200 mg n=43 Any AE, n (%) 69 (33.8) 32 (30.8) 24 (55.8) Severe AE, n (%) 4 (2.0) 2 (1.9) 2 (4.7) Discontinuation because of AE, n (%) 2 (1.0) 3 (2.9) 2 (4.7) Most frequently reported TEAE of any cause (>5% in any treatment group), n (%) Nasopharyngitis 8 (3.9) 6 (5.8) 3 (7.0) Upper respiratory tract infection 17 (8.3) 2 (1.9) 2 (4.7) Dermatitis atopic 7 (3.4) 4 (3.8) 3 (7.0) TEAEs of special interest Herpes zoster 2 (1.0) 4 (3.8) 2 (4.7) Thrombocytopenia 0 0 0 AE, adverse event; TEAE, treatment-emergent adverse event. CONCLUSION • Rescue therapy with abrocitinib 200 mg + topical medicated therapy recaptured response in a large proportion of patients who experienced flare during the maintenance period of JADE REGIMEN and was associated with an acceptable safety profile REFERENCES 1. Boguniewicz M et al. Ann Allergy Asthma Immunol. 2018;120:10-22. 2. Blauvelt A et al. J Am Acad Dermatol. 2022;86:104-112. ACKNOWLEDGMENTS Editorial/medical writing support under the guidance of the authors was provided by Megan Elder, 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). This study was funded by Pfizer Inc. Previously presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting; February 25-28, 2022; Phoenix, Arizona. Efficacy of Abrocitinib Rescue Therapy in the Phase 3 Study JADE REGIMEN Jonathan I. Silverberg,1 Mark Boguniewicz,2 Kim Papp,3 Athanasios Tsianakas,4 Pinaki Biswas,5 Claire Feeney,6 Mark Levenberg7 1The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; 2National Jewish Health and University of Colorado School of Medicine, Denver, CO, USA; 3K. Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada; 4Fachklinik Bad Bentheim, Bad Bentheim, Germany; 5Pfizer Inc., New York, NY, USA; 6Pfizer Ltd., Surrey, United Kingdom; 7Pfizer Inc., Collegeville, PA, USA DISCLOSURES JIS served as an investigator for Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Menlo Therapeutics, Realm Therapeutics, Regeneron, and Sanofi; as a consultant for Pfizer Inc., AbbVie, Anacor, AnaptysBio, Arena Pharmaceuticals, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Realm Therapeutics, Regeneron, and Sanofi-Genzyme; and as a speaker for Regeneron and Sanofi-Genzyme. MB has been an investigator for Regeneron and Incyte and advisor for Pfizer Inc., AbbVie, Eli Lilly and Company, Incyte, Janssen, LEO Pharma, Regeneron, and Sanofi-Genzyme. KP has been a consultant, scientific adviser, investigator, scientific officer, and/or speaker for Pfizer Inc., AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Bausch Health, Boehringer Ingelheim, BMS, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly and Company, Forward Pharma, Galderma, Genentech, Gilead, GlaxoSmithKline, Janssen, Kyowa Hakka Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck Sharp & Dahme, Merck-Serano, Mitsubishi Pharma, Novartis, PRCL Research, Regeneron, Roche, Sanofi-Aventis/Genzyme, Sun Pharma, Takeda, UCB, and Valeant. AT had nothing to declare PK, CF, and ML are employees and stockholders of Pfizer Inc.