FDA Approval Announcement
On September 9, 2022, Bristol-Myers Squibb announced that the U.S. Food and Drug Administration (FDA) approved Sotyktu (deucravacitinib) for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu is an oral, highly selective, first-in-class allosteric inhibitor of tyrosine kinase 2 (TYK2). Concomitant use of Sotyktu with other potent immunosuppressive agents is not recommended.
Basis for Approval: Phase 3 POETYK PSO Trials
The approval was based on results from two global, multicenter, double-blind, randomized Phase 3 clinical trials, POETYK PSO-1 (n=664) and POETYK PSO-2 (n=1020), which evaluated the efficacy and safety of Sotyktu compared with apremilast and placebo in adult patients with moderate to severe plaque psoriasis.
Primary Endpoints
The co-primary endpoints were the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI) score (PASI 75) and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear skin) at Week 16. PASI 75 is defined as an improvement of at least 75% from baseline in the PASI score.
Efficacy Results
Efficacy of Sotyktu was demonstrated at Weeks 16 and 24, with durable responses maintained through Week 52. Sotyktu exhibited a favorable safety and tolerability profile.
Week 16 Efficacy Outcomes
The proportion of patients achieving PASI 75 was 58.7% and 53.6% in the Sotyktu groups, 12.7% and 9.4% in the placebo groups, and 35.1% and 40.2% in the apremilast groups. The proportion of patients achieving sPGA 0/1 was 53.6% and 50.3% in the Sotyktu groups, 7.2% and 8.6% in the placebo groups, and 32.1% and 34.3% in the apremilast groups.
Week 24 Efficacy Outcomes
The proportion of patients achieving PASI 75 was 69.0% and 59.3% in the Sotyktu groups, and 38.1% and 37.8% in the apremilast groups. The proportion of patients achieving sPGA 0/1 was 58.4% and 50.4% in the Sotyktu groups, and 31.0% and 29.5% in the apremilast groups.
Safety Profile
In the POETYK PSO trials, the most common adverse reactions (≥1%) in Sotyktu-treated patients at Week 16 were upper respiratory tract infection (19.2%), elevated blood creatine phosphokinase (2.7%), herpes simplex (2.0%), oral ulceration (1.9%), folliculitis (1.7%), and acne (1.4%).
Clinical Significance of Sotyktu
Psoriasis is a chronic systemic immune-mediated disease. Sotyktu is the first oral therapy approved for psoriasis in nearly a decade and represents a once-daily oral systemic treatment option. Unlike topical therapies applied directly to the skin, Sotyktu minimizes systemic inflammation. Its mechanism of action differs from existing systemic agents, including other oral therapies and biologics that require administration via injection.
