101102042_Cobi_Pop_PK_L1a Presented at the Winter Clinical Dermatology Conference; January 13-18, 2023; Kohala Coast, Hawaii Copies of this poster and supplemental information, which can be 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 • Abrocitinib is an oral, once-daily, Janus kinase 1–selective inhibitor approved for the treatment of with moderate-to-severe AD1-3 • An integrated safety analysis was previously published for abrocitinib clinical trials that included 2856 patients with moderate-to-severe AD4 • Additional safety data have accrued from further randomized controlled trials and an ongoing long-term extension study • The integrated safety analysis presented here includes data from the largest population and longest follow-up period reported to date OBJECTIVE • To evaluate the long-term safety profile of abrocitinib and provide relevant information for practitioners METHODS Study Design • Data from patients who received ≥1 dose of abrocitinib 200 mg or 100 mg in the JADE clinical trial program were pooled into 2 cohorts (Figure 1) – In the consistent-dose cohort, patients received the same abrocitinib dose during the entire exposure time in parent phase 3 studies and/ or the long-term extension study JADE EXTEND (NCT03422822); data cutoff April 16, 2021 • Parent studies were JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367), and JADE REGIMEN (NCT03627767) ◦ For JADE REGIMEN (200 mg only), only patients from the open-label run-in phase who did not subsequently enter the randomized phase were included • Patients may have received their first dose of abrocitinib in JADE EXTEND if they previously received placebo in the placebo- controlled parent studies and/or dupilumab in JADE COMPARE or JADE DARE • Patients from the phase 2b study (NCT02780167) who received abrocitinib 200 mg or 100 mg were also included – In the variable-dose cohort, patients received different doses of abrocitinib (200 mg and 100 mg) throughout exposure time in the parent study (JADE REGIMEN) and were enrolled in JADE EXTEND • Patients who completed the open-label period of JADE REGIMEN (abrocitinib 200 mg only) and entered the randomized phase (abrocitinib 200 mg, abrocitinib 100 mg, or placebo) were included • Some patients subsequently entered the JADE REGIMEN rescue phase (abrocitinib 200 mg) and/or JADE EXTEND (abrocitinib 200 mg or 100 mg) Figure 1. Analysis Cohorts Data cutoff: April 16, 2021Time Consistent-Dose Cohort Variable-Dose Cohort JADE DARE JADE REGIMEN (open-label run-in) JADE REGIMEN (open-label rescuec) JADE REGIMEN (open-label run-inb) JADE EXTENDa JADE EXTENDa JADE MONO-1 JADE MONO-2 JADE COMPARE JADE TEEN Phase 2b Parent Studies Phase 3 Placebo Controlled Trials JADE REGIMEN (randomized) Placebo Abrocitinib 100 mg QD Abrocitinib 200 mg QD JADE EXTEND EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; QD, once-daily. JADE EXTEND is ongoing. a Includes patients who received their first dose of abrocitinib (100 mg or 200 mg) in JADE EXTEND after receiving placebo in a phase 3 placebo-controlled trial or dupilumab in JADE COMPARE or JADE DARE. b Patients in the open-label run-in period who achieved response (IGA score of 0 [clear] or 1 [almost clear] and ≥75% improvement from baseline on the EASI) after 12 weeks of treatment with abrocitinib 200 mg were randomly allocated to treatment with abrocitinib 200 mg, abrocitinib 100 mg, or placebo. c Patients who experienced a flare (≥50% loss of week 12 EASI response and new IGA score of ≥2) during the randomized period entered the open-label rescue period (abrocitinib 200 mg plus topical medicated treatment). Statistical Analysis • Incidence rates (IRs; number of unique patients with events per 100 patient-years [PY]) of adverse events were calculated – For IR calculations, patient exposure was calculated up to the time of first event for patients with events – Time to event was censored at the end of the risk period for patients who did not experience an event • A Cox proportional hazard regression analysis evaluated risk factors for specific events of interest RESULTS Patients • Data from 3582 patients were analyzed, representing 4313.4 PY – The consistent-dose cohort (n=2784) included 1721.3 PY of exposure to abrocitinib 200 mg (n=1761) and 1284.4 PY of exposure to abrocitinib 100 mg (n=1023) • Duration of exposure was ≥48 weeks in 767 of 1761 patients (43.6%) and 684 of 1023 patients (66.9%) and ≥96 weeks in 317 of 1761 patients (18.0%) and 237 of 1023 patients (23.2%) in patients treated with abrocitinib 200 mg and 100 mg, respectively – In the variable-dose cohort (n=798), total abrocitinib exposure was 1307.7 PY; cumulative abrocitinib exposure was ≥48 weeks in 687 of 798 patients (86.1%) and ≥96 weeks in 362 of 798 patients (45.4%) • In the consistent-dose and variable-dose cohorts, median age was 30.0 and 29.0 years, 490 patients (17.6%) and 145 patients (18.2%) were adolescents, and 143 patients (5.1%) and 30 patients (3.8%) were aged ≥65 years at screening, respectively (Supplementary Table S1, accessible via the QR code) Safety Events • IRs for SAEs, AEs leading to treatment discontinuation, deaths, and other specific adverse events of interest are reported in Figure 2 for the consistent-dose cohort and in Supplementary Figure S1 for the variable-dose cohort – IRs for SAEs were higher in patients aged ≥65 years versus younger patients in the consistent-dose cohort – Serious infections were the most frequent SAEs reported in both the consistent-dose cohort and the variable-dose cohort – IRs for TEAEs leading to discontinuation were higher with abrocitinib 200 mg than with abrocitinib 100 mg • 7 deaths were reported in the consistent-dose cohort, including 5 in the abrocitinib 200 mg group (coronavirus disease 2019 [COVID-19], n=2; septic shock, n=1; cardiac failure, n=1; cardiorespiratory arrest, n=1) and 2 in the abrocitinib 100 mg group(sudden death, n=1; COVID-19, n=1); 2 of the deaths described here were previously reported. There was also an additional death (>200 days after last dose of abrocitinib) that was previously reported which involved gastric adenocarcinoma4 – No deaths were reported in the variable-dose cohort Infections • IRs for infections are reported in Figure 2 for the continuous-dose cohort and in Supplementary Figure S1 for the variable-dose cohort • Herpes zoster, herpes simplex, and pneumonia were the most frequent serious infections – Most (95%) adjudicated opportunistic herpes zoster infections were cutaneous; 2 (5%) were extracutaneous (1 serious disseminated varicella zoster virus infection, 1 serious herpes zoster meningitis) – A trend towards a dose-dependent relationship was observed with herpes zoster infections • No risk factors were identified for serious infections in a Cox regression analysis • Potential risk factors for treatment-emergent herpes zoster included abrocitinib dose, age ≥65 years, medical history of herpes zoster, absolute lymphocyte count <1000/mm3 prior to infection, and region (Supplemental Table S2) Malignancies and Cardiovascular Events • IRs for malignancies and cardiovascular events are reported in Figure 2 for the continuous-dose cohort, and in Supplementary Figure S1 for the variable-dose cohort – IRs were higher in patients aged ≥65 years compared with younger patients Hematological Events • IRs for thrombocytopenia and lymphopenia are reported in Figure 2 for the continuous-dose cohort and in Supplementary Figure S1 for the variable-dose cohort – IRs for thrombocytopenia and lymphopenia events were higher in patients aged ≥65 years compared with younger patients Safety of Abrocitinib in 3582 Patients With Moderate-to-Severe Atopic Dermatitis With Over 900 Patients Exposed for Almost 2 Years Eric L. Simpson,1 Jonathan I. Silverberg,2 Audrey Nosbaum,3 Kevin Winthrop,1 Emma Guttman-Yassky,4 Karin M. Hoffmeister,5 Alexander Egeberg,6 Hernan Valdez,7 Haiyun Fan,8 Saleem A. Farooqui,9 Gary Chan,10 Justine Alderfer,8 William Romero,11 Susan Johnson12 1Oregon Health & Science University, Portland, OR, USA; 2The George Washington University School of Medicine & Health Sciences, Washington, DC, USA; 3Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, France; 4Icahn School of Medicine, Mount Sinai Medical Center, New York, NY, USA; 5Translational Glycomics Center, Versiti Blood Research Institute, Milwaukee, WI, USA; Medical College of Wisconsin, Milwaukee, WI, USA; 6Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; 7Pfizer Inc., New York, NY, USA; 8Pfizer Inc., Collegeville, PA, USA; 9Pfizer R & D UK Ltd., Sandwich, Kent, United Kingdom; 10Pfizer Inc., Groton, CT, USA; 11Pfizer Ltd., Tadworth, Surrey, United Kingdom; 12Pfizer Inc., Raleigh-Durham, NC, USA Figure 2. IRs (95% CI) for Adverse Events of Special Interest in the Consistent-Dose Cohort 2 30 5 101 154 IR, Number of Patients With Events per 100 PY Deaths TEAEs resulting in permanent discontinuation SAEs Serious herpes zoster Adjudicated opportunistic herpes zoster Serious infections Serious eczema herpeticum Serious herpes simplex Adjudicated turberculosis Adjudicated MACE Adjudicated NMSC Adjudicated malignancies (excluding NMSC) Adjudicated non fatal VTEa Rhabdomyolysis Lymphopenia Thrombocytopenia (confirmed platelet count <75 × 103/mm3) Retinal detachment Abrocitinib 100 mg QD (n=1023) Abrocitinib 200 mg QD (n=1761) IR (95% CI) 6.31 (5.01-7.84) 7.28 (6.07-8.67) 8.64 (7.12-10.38) 13.00 (11.37-14.79) 0.15 (0.02-0.55) 0.28 (0.09-0.65) 2.43 (1.66-3.44) 2.46 (1.79-3.31) 0.61 (0.26-1.20) 1.23 (0.77-1.87) 0.15 (0.02-0.55) 0.50 (0.23-0.95) 0.08 (0.00-0.42) 0.11 (0.01-0.40) 0.38 (0.12-0.88) 0.06 (0.00-0.31) 0.00 (0.00-0.28) 0.06 (0.00-0.31) 0.08 (0.00-0.42) 0.33 (0.12-0.73) 0.38 (0.12-0.89) 0.17 (0.03-0.49) 0.15 (0.02-0.55) 0.22 (0.06-0.57) 0.08 (0.00-0.42) 0.28 (0.09-0.65) 0.00 (0.00-0.28) 0.45 (0.19-0.88) 0.00 (0.00-0.28) 0.56 (0.27-1.02) 0.00 (0.00-0.28) 0.06 (0.00-0.31) 0.15 (0.02-0.55) 0.11 (0.01-0.40) IR, incidence rate; MACE, major adverse cardiac events; NMSC, non-melanoma skin cancer; PY, person-years; QD, once-daily; SAE, serious adverse events; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism. a1 pulmonary embolism embolism event (not adjudicated) was included. CONCLUSIONS • For patients requiring Janus kinase inhibitors to control moderate-to- severe AD, these data further clarify the overall long-term safety profile of abrocitinib – In this largest and longest analysis of abrocitinib in patients with moderate-to-severe AD to date, the AEs identified were generally consistent with previous safety analyses4,5 • Patient selection and dose selection are important considerations for prescribers – Risk of SAEs, herpes zoster infection, malignancies, cardiovascular events, lymphopenia, and thrombocytopenia increased in patients aged ≥65 years – Increased risk of herpes zoster also appeared to be related to higher abrocitinib dose, medical history of herpes zoster, geographic region, and absolute lymphocyte count <1000/mm3 prior to infection • These data support the acceptable safety profile of abrocitinib in the treatment of moderate-to-severe AD in eligible patients REFERENCES 1. Cibinqo (abrocitinib). Summary of product characteristics. European Medicines Agency; December 17, 2021. 2. Cibinqo (abrocitinib) tablets. Prescribing information. Pfizer Labs; January 2022. 3. Cibinqo (abrocitinib), 100 mg film-coated tablets. Summary of product characteristics. Pfizer Ltd.; September 10, 2021. 4. Simpson EL et al. Am J Clin Dermatol. 2021;22:693-707. 5. Cork MJ et al. Presented at: European Academy of Dermatology and Venereology (EADV) Congress; September 29-October 2, 2021; Berlin, Germany. ACKNOWLEDGMENTS Editorial/writing support under the guidance of authors was provided by Megan K. Elder, PhD, at ApotheCom (San Francisco, CA), 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 funded by Pfizer Inc. Previously presented at the 31st European Academy of Dermatology and Venereology (EADV) Hybrid Congress; September 7-10, 2022; Milan, Italy. DISCLOSURES ES received grants from Pfizer Inc., Eli Lilly and company, Kyowa Kirin, LEO Pharma, Merck, and Regeneron and personal fees from Pfizer Inc., Bausch Health (Valeant), Dermira, Eli Lilly and company, Galderma, LEO Pharma, Menlo Therapeutics, Novartis, Regeneron, and Sanofi Genzyme. JIS served as an investigator for Celgene, Eli Lilly and company, F. Hoffmann-LaRoche, 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; and as a speaker for Regeneron and Sanofi. AN is an investigator for AbbVie, Eli Lilly and company, Incyte, LEO Pharma, Novartis, and Sanofi; a consultant for Pfizer Inc., AbbVie, Eli Lilly and company, Galderma, LEO Pharma, Novartis, and Sanofi; a speaker for AbbVie, Regeneron, and Sanofi; and is on advisory boards for Pfizer Inc., AbbVie, LEO Pharma, and Sanofi. KW reports research grants from Pfizer Inc. and Bristol Myers Squibb, and consulting fees from Pfizer Inc., AbbVie, Union Chimique Belge (UCB), Eli Lilly and company, Galapagos, Novartis, Regeneron, Sanofi, Stiefel/GlaxoSmithKlin, Vitae, (honorarium);as a consultant for Pfizer Inc., AbbVie, Almirall (honorarium), Anacor, Asana Biosciences, Celgene, Dermira, Eli Lilly and company, Galderma, Glenmark, Kiowa Kirin, LEO Pharmaceuticals, MedImmune, Mitsubishi Tanabe, Novartis, Regeneron, Sanofi, Stiefel/GlaxoSmithKlin, and Vitae; and as an investigator for Celgene, Eli Lilly and company (grants to institution), LEO Pharmaceuticals, MedImmune, and Regeneron. KMH received honoraria as consultant from Pfizer Inc. and Platelet Biogenesis. AE has received research funding from Pfizer Inc., AbbVie, Bristol-Myers Squibb, Danish National Psoriasis Foundation, Eli Lilly and company, Janssen Pharmaceuticals, Kgl Hofbundtmager Aage Bang Foundation, and Novartis; and has received honoraria as a consultant and/or speaker from Pfizer Inc., AbbVie, Almirall, Bristol-Myers Squibb, Dermavant, Eli Lilly and company, Galápagos NV, Galderma, Janssen Pharmaceuticals, LEO Pharma, Mylan, Novartis, Samsung Bioepis Co., Ltd., Sun Pharmaceuticals, UCB, Union Therapeutics, and Zuellig Pharma Ltd. HV was an employee and shareholder of Pfizer, Inc. at the time this analysis was conducted. HF, SAF, GC, JA, WR, and SJ are employees and shareholders of Pfizer, Inc.