Key Takeaways:
• Socrodeucitinib 12 mg once daily achieved PASI 75 in 72.1% of patients at week 12 versus 7.5% with placebo (P <.001).
• Responses were dose-dependent across PASI 50, PASI 90, PASI 100 and sPGA 0/1 outcomes, all statistically significant versus placebo at 12 mg.
• Adverse events were more common with socrodeucitinib, most frequently upper respiratory tract infection, but serious adverse events and discontinuations were infrequent.
• No deaths, major adverse cardiovascular events, malignancies or clinically meaningful laboratory abnormalities were reported.
• The 12 mg once-daily dose has advanced into an ongoing phase 3 trial (NCT06672393).
Socrodeucitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, achieved significantly higher rates of psoriasis area and severity index (PASI) 75 response at Week 12 compared with placebo in a phase 2 randomized trial of individuals with moderate to severe plaque psoriasis, according to data published in the Journal of the European Academy of Dermatology and Venereology.¹
TYK2 inhibitors have emerged as a differentiated oral option in the systemic psoriasis landscape, positioned as more selective than JAK1/2/3 inhibitors, which carry boxed warnings for cardiovascular events, malignancy and infection. Deucravacitinib and TAK-279 previously demonstrated the clinical potential of pseudokinase-directed TYK2 inhibition, and socrodeucitinib (HS-10374) adds phase 2 data supporting a 12 mg once-daily dose ahead of an ongoing phase 3 program.²
Socrodeucitinib Trial Design and PASI 75 Results
The phase 2, randomized, double-blind, placebo-controlled trial enrolled 125 patients across 38 centers in China between September 2023 and April 2024. Patients were stratified by prior biologic use and randomized 1:1:1 to receive oral socrodeucitinib at 6 mg, 12 mg or placebo once-per-day for 12 weeks.
Eligible adults were 18 to 70 years old with plaque psoriasis for 6 months or longer, a static Physician's Global Assessment (sPGA) score of 3 or higher, a PASI score of 12 or higher and body surface area involvement of 10% or greater. Baseline characteristics were balanced across arms, with a mean PASI score of 20.0 and 26.4% of patients previously treated with a biologic agent.
At Week 12, PASI 75 was achieved by 72.1% of patients on the 12 mg dose and 28.6% on the 6 mg dose, compared with 7.5% on placebo (12 mg, P <.001; 6 mg, P = .013). The proportion difference versus placebo was 65.2 percentage points at the 12 mg dose (95% CI, 50.07-80.34) and 21.2 percentage points at the 6 mg dose (95% CI, 5.47-36.96). Responses emerged as early as Week 4 and were sustained through Week 12 at both doses.
Socrodeucitinib Secondary Endpoints and Safety Profile
Secondary endpoints tracked the primary result at the 12 mg dose. PASI 90 was achieved by 46.5% of patients versus 0% on placebo (P <.001), and PASI 100 by 11.6% versus 0% (P = .027).
