Journal Article

AB0530 DESIGN OF 2 PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, GLOBAL TRIALS OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYROSINE KINASE 2 (TYK2) INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

Van Vollenhoven, R., Delev, N., Wegman, T., Stevens, A., Morand, E. F., Shah, V., Davey, M., Askanase, A., Furie, R., Connors, K., Hobar, C., Arriens, C.

2023

Overview

BackgroundDeucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis [1,2]. Deucravacitinib demonstrated efficacy across the primary endpoint and all key secondary endpoints in a phase 2 trial in patients with systemic lupus erythematosus (SLE) [3].ObjectivesHere, we describe 2 phase 3 trials currently underway to assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and rigorous management structure [3].MethodsIn these phase 3, randomized, double-blind, placebo-controlled, global trials (POETYK SLE-1 [NCT05617677], POETYK SLE-2 [NCT05620407]), adults (aged 18-75) with active SLE on background standard-of-care treatment will be randomized (1:1) to placebo or deucravacitinib for 52 weeks of double-blind treatment (Figure 1). Patients on glucocorticoids will be instructed to taper, unless significant disease activity is present, to a threshold dose level during the double-blind treatment period. At week 52, patients may choose to continue in a 104-week open-label extension phase, in which all patients receive deucravacitinib. Key eligibility criteria and study design are depicted below (Figure 1). The primary endpoint of SLE Responder Index (SRI[4]) and all secondary endpoints will be assessed at week 52 (Table 1). Safety and tolerability will be assessed throughout the trial.ResultsPlanned randomization in each trial includes 490 patients (245 per treatment group) in 27 countries across North and South America, Europe, and Asia-Pacific.ConclusionThe phase 3 POETYK SLE trials will further evaluate the efficacy and safety of deucravacitinib, an oral, selective, TYK2 inhibitor, in patients with active SLE.References[1]Armstrong A, et al. J Am Acad Dermatol. 2022;S0190-9622(22)02256-3.[2]Strober B, et al. J Am Acad Dermatol. 2022;S0190-9622(22)02643-3.[3]Morand E, et al. Arthritis Rheumatol. 2022; Nov 11 (Epub ahead of print). doi: 10.1002/art.42391.Table 1.Primary and Secondary Endpoints Assessed at Week 52Primary Endpoint • Proportion of patients who achieve an SLE Responder Index (SRI[4]) responseSecondary Endpoints • Proportion of patients who achieve a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response • Proportion of patients with simultaneous achievement of SRI(4) and BICLA response (dual responders) • Proportion of patients who achieve a ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50) among patients with CLASI activity score ≥ 10 at baseline • Proportion of patients who achieve Lupus Low Disease Activity State (LLDAS) • Proportion of patients maintaining ≤ 7.5 mg/day glucocorticoid dose from weeks 24 to 52 • Proportion of patients who achieve a ≥ 50% reduction in active joints (Joint-Count 50) among patients with ≥ 6 active joints at baseline • Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scoreAcknowledgementsThis study was sponsored by Bristol Myers Squibb.Disclosure of InterestsCristina Arriens Speakers bureau: AstraZeneca, Aurinia, Bristol Myers Squibb, GlaxoSmithKline, Kezar, AstraZeneca and Aurinia, Grant/research support from: AstraZeneca and Bristol Myers Squibb, Anca Askanase Consultant of: Abbvie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, GlaxoSmithKline, Idorsia, Janssen, Pfizer, and UCB, Richard Furie Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Eric F. Morand Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Novartis, and Servier, Grant/research support from: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, and UCB, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, Janssen, Pfizer, UCB, Consultant of: UCB, Pfizer, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, AbbVie, Galapagos, and Janssen, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Pfizer, UCB, Roche, and GlaxoSmithKline, Kevin Connors Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Monica Davey Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Vaishali Shah Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Anna Stevens Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Wegman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Coburn Hobar Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Allosteric properties / Antineutrophil cytoplasmic antibodies / Clinical Trials / Cutaneous Lupus Erythematosus / Double-blind studies / Enzyme inhibitors / Glucocorticoids / Joint diseases / Lupus / Placebos / Protein-tyrosine kinase / Psoriasis / Safety / Scientific Abstracts / Stockholders / Systemic lupus erythematosus / Tyk2 protein