2134: Deucravacitinib Long-term Efficacy and Safety in Plaque Psoriasis: 2-Year Results from the Phase 3 POETYK PSO Program

Richard Warren¹, Howard Sofen², Shinichi Imafuku³, Jacek C. Szepietowski⁴, Andrew Blauvelt⁵, Lynda Spelman⁶, Jessica Toms⁷, Alex Buck⁸, Subhashis Banerjee⁷ and Alan Menter⁹, ¹The University of Manchester, Manchester, United Kingdom, ²UCLA School of Medicine, Los Angeles, CA, ³Fukuoka University Hospital, Fukuoka, Japan, ⁴Wroclaw Medical University, Wroclaw, Poland, ⁵Oregon Medical Research Center, Portland, OR, USA, Portland, OR, ⁶Veracity Clinical Research, Woolloongabba, Australia, ⁷Bristol Myers Squibb, Princeton, NJ, ⁸Bristol Myers Squibb; Cytel Inc, Princeton, ⁹Baylor University Medical Center, Dallas, TX

Background/Purpose: Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signalling of key cytokines (eg, IL-23 and Type I IFN) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and PsA. Deucravacitinib is an oral, selective, allosteric TYK2 inhibitor that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a phase 2 trial in patients with PsA.¹ The efficacy and tolerability of deucravacitinib in patients with moderate to severe psoriasis were previously demonstrated in 2 pivotal, phase 3, double-blind trials, POETYK PSO-1 and PSO-2.² The long-term efficacy and safety of deucravacitinib were assessed in patients with psoriasis enrolled in the phase 3, double-blind POETYK PSO-1 and PSO-2 trials and the open-label long-term extension (LTE) trial.

Methods: The 52-week PSO-1 and PSO-2 trials (NCT03624127 and NCT03611751) randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients completing PSO-1 or PSO-2 could then enroll in the LTE trial (NCT04036435) and receive open-label deucravacitinib 6 mg once daily. All 3 trials overlapped with the COVID-19 pandemic. Efficacy outcomes are reported for patients (n = 1221) who received ≥1 dose of deucravacitinib in the LTE using a modified nonresponder imputation approach. Safety data are reported for patients who received ≥ 1 dose of deucravacitinib during the controlled weeks 0–52 period (n = 1364; 969.0 person-years [PY]) and during the cumulative PSO-1/PSO-2 and LTE period (n = 1519; 2482.0 PY).

Results: Demographic and disease characteristics were balanced across treatment groups; mean age at disease onset was 28.6 years, mean disease duration was 18.9 years at last visit of the parent trials, and 18.0% of patients had PsA at baseline of the parent trials. At enrollment in the LTE trial, response rates for ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) were 71.3% and 56.3%, respectively, and were maintained through LTE week 60 (PASI 75, 75.7%; sPGA 0/1, 57.1%). Exposure-adjusted incidence rates per 100 PY were similar in the controlled (weeks 0‒52) and cumulative (PSO-1, PSO-2, and LTE) trial periods for adverse events (229.2 and 154.4, respectively), serious adverse events (5.7 and 6.1), discontinuations (4.4 and 2.8), deaths (0.2 and 0.4), herpes zoster (0.9 and 0.7), malignancies (1.0 and 0.9), major adverse cardiovascular events (0.3 and 0.4), and venous thromboembolism (0.1 and 0.1).

Conclusion: Deucravacitinib demonstrated persistent efficacy and consistent safety profiles in patients with psoriasis for up to 2 years after initial randomization in the POETYK PSO‑1, PSO-2, and LTE trials.

References
1. Mease PJ, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase 2 trial in psoriatic arthritis. Ann Rheum Dis. 2022;81:815-822.
2. Armstrong A, et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.

Disclosures: R. Warren, AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB Pharma, DiCE, Union; H. Sofen, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, Sun Pharma; S. Imafuku, AbbVie, Eisai, Janssen, Kyowa Kirin, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, Torii Yakuhin, Amgen, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, UCB; J. Szepietowski, AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, Trevi, Eli Lilly, Janssen-Cilag, Amgen, Bristol Myers Squibb, Galapagos,, Galderma, Incyte, InfraRX, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB; A. Blauvelt, AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome; L. Spelman, AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne Pharma, MedImmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, Zai Lab; J. Toms, Bristol Myers Squibb; A. Buck, Bristol Myers Squibb; S. Banerjee, Bristol Myers Squibb; A. Menter, Abbott Labs, Amgen, Boehringer Ingelheim, Janssen Biotech, Leo Pharma, Eli Lilly, Novartis, Sun Pharma, UCB, Celgene, Merck.