Deucravacitinib long-term efficacy with continuous treatment in plaque psoriasis: 2-year results from the phase 3 POETYK PSO program Mark Lebwohl,1 Richard B Warren,2 Howard Sofen,3 Shinichi Imafuku,4 Carle Paul,5 Jacek C Szepietowski,6 Lynda Spelman,7 Thierry Passeron,8 Elizabeth Colston,9 Lauren Hippeli,9 Andrew Napoli,9 Renata M Kisa,9 Subhashis Banerjee,9 Alan Menter,10 Diamant Thaçi,11 Andrew Blauvelt12 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Dermatology Centre, Salford Royal NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK; 3UCLA School of Medicine, Los Angeles, CA, USA; 4Fukuoka University Hospital, Fukuoka, Japan; 5Toulouse University and CHU, Toulouse, France; 6Wrocław Medical University, Wrocław, Poland; 7Veracity Clinical Research, Brisbane, QLD, Australia; 8Côte d’Azur University, University Hospital of Nice, Nice, France; 9Bristol Myers Squibb, Princeton, NJ, USA; 10Baylor University Medical Center, Dallas, TX, USA; 11University of Lübeck, Lübeck, Germany; 12Oregon Medical Research Center, Portland, OR, USA Presented at the Winter Clinical Dermatology Conference - Hawaii®; January 13-18, 2023; Kohala Coast, HI This is an encore of the 2022 31st EADV Congress presentation Email: lebwohl@aol.com Copies of this poster are for personal use only and may not be reproduced without written permission from the authors. Synopsis • Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates signaling of cytokines (eg, interleukin-23, Type I interferons) involved in psoriasis pathogenesis1 • Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy2 • Deucravacitinib binds to the TYK2 regulatory domain rather than to the more conserved catalytic domain where Janus kinase (JAK) 1/2/3 inhibitors bind1 (Figure 1) Figure 1. Mechanism of action of deucravacitinib TYK2 Deucravacitinib (allosteric inhibitor class) Unique TYK2 regulatory domain Catalytic domain (highly conserved across JAK family) ATP-binding active site (approved JAK inhibitor class) •  ≥100-fold greater selectivity for TYK2 vs JAK 1/3 • ≥2000-fold greater selectivity for TYK2 vs JAK 2 Selectivity in cells1,3: ATP, adenosine 5′-triphosphate; JAK, Janus kinase; TYK2, tyrosine kinase 2. • Deucravacitinib was studied at 6 mg once daily in two global phase 3 pivotal trials, POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751)4,5 — Only POETYK PSO-1 included a continuous deucravacitinib treatment arm from Day 1 to Week 52 — Placebo patients crossed over to deucravacitinib at Week 16 in both trials • POETYK PSO-1 demonstrated (Figure 26): — Significantly greater response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician’s Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline (sPGA 0/1) at Week 16 with deucravacitinib vs placebo and apremilast4 — Clinical efficacy that was maintained through Week 52 with continuous deucravacitinib treatment7 • Patients completing the POETYK PSO-1 trial could enroll in the POETYK long-term extension (LTE) trial and receive open-label deucravacitinib 6 mg once daily • The 2-year safety profile of deucravacitinib in the POETYK LTE trial was consistent with that observed from Weeks 0–52 of the POETYK PSO-1 and PSO-2 trials, and there were no emerging safety signals8 Figure 2. Clinical efficacy in POETYK PSO-1 (NRI)6 Deucravacitinib (n = 332) Placebo crossoversa (n = 145)Placebo (n = 166) sPGA 0/1 58.4% 69.3% 65.1% 12.7% 44.1% 68.3% 0 25 50 75 100 PASI 75 53.6% 58.7% 52.7% 7.2% 39.3% 53.8% 0 25 50 75 100 Week 16 Week 24 Week 52 n = 194 21 64230 99216 Week 16 Week 24 Week 52 n = 178 12 57195 78175 % o f p at ie n ts % o f p at ie n ts aPatients initially randomized to placebo crossed over to deucravacitinib at Week 16. NRI, nonresponder imputation; PASI 75, ≥75% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician’s Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline. Objectives • To examine long-term efficacy responses in POETYK PSO-1 patients who: — Received continuous deucravacitinib treatment from Day 1 and entered the POETYK LTE — Achieved PASI 75 response on deucravacitinib at Week 16, continued on deucravacitinib, and entered the POETYK LTE Methods Study designs and analysis populations • The study designs for the POETYK PSO-1 and LTE trials are illustrated in Figure 3 • Patients meeting the following criteria were eligible to enroll in the study: — Age ≥18 years — Diagnosis of moderate to severe plaque psoriasis • Baseline PASI ≥12, sPGA ≥3, and body surface area involvement ≥10% • Patient randomization in POETYK PSO-1 was stratified by geographic region, body weight, and prior biologic use • Analysis populations were defined as: — Continuous deucravacitinib treatment from baseline: patients who received continuous deucravacitinib from Day 1 (Week 0) and entered the POETYK LTE • Since results with nonresponder imputation (NRI) were shown earlier from Weeks 0–52,4,5 only Weeks 52–112 results are shown here — Continuous deucravacitinib Week 16 PASI 75 responders: patients who received continuous deucravacitinib from Day 1, achieved PASI 75 at Week 16, and entered the POETYK LTE Figure 3. POETYK PSO-1 and LTE study designs 100 POETYK PSO-1 Deucravacitinib 6 mg QD Placebo (n = 166) Deucravacitinib 6 mg QD Apremilast 30 mg BID Titrate* P O E T Y K P SO -1 1 :2 :1 r an d o m iz at io n Deucravacitinib 6 mg QD (n = 332) Apremilast 30 mg BIDa (n = 168) Cumulative exposure (weeks) 16 24 520 Primary endpoint B LI N D E D S W IT C H T O O P E N -L A B E L D E U C R A V A C IT IN IB Open-label deucravacitinib 6 mg QDb POETYK LTE 14856 60 68 76 88 112 124 1364 8 12 20 28 32 36 40 44 48 480 964 8 16 24 36 60 72 84Exposure relative to LTE (weeks)