A randomized phase 2 trial of socrodeucitinib in moderate‐to‐severe plaque psoriasis

BACKGROUND: Tyrosine kinase 2 (TYK2), a key part of the inflammatory cascade responses, plays an integral role in the pathogenesis of psoriasis. Socrodeucitinib, an oral, TYK2 allosteric inhibitor, selectively inhibits TYK2 cytokine signalling pathways in psoriasis pathogenesis. OBJECTIVES: To evaluate the efficacy and safety of socrodeucitinib in patients with moderate-to-severe plaque psoriasis. METHODS: In this phase 2, double-blind, placebo-controlled trial, 125 patients were randomly assigned (1:1:1) to receive socrodeucitinib at 6 mg, 12 mg or placebo orally, once daily, for 12 weeks. The primary endpoint was the proportion of patients with a 75% or greater reduction from the baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. RESULTS: At week 12, significantly more patients treated with socrodeucitinib achieved a 75% reduction from baseline in PASI score compared with placebo (28.6% at 6 mg, 72.1% at 12 mg vs. 7.5% for placebo, p < 0.05 and p < 0.001, respectively). At the 12 mg dose, socrodeucitinib resulted in significantly higher response rates compared to placebo, with 46.5% of patients achieving PASI 90 (p < 0.001) and 11.6% achieving PASI 100 (p < 0.05). The treatment of socrodeucitinib also led to significantly higher proportions of patients achieving sPGA responses of 0 or 1 compared to placebo: 33.3% at 6 mg and 65.1% at 12 mg versus 10% for placebo (p < 0.05 and p < 0.001, respectively). Most common adverse events included upper respiratory tract infection which demonstrated a certain dose dependency. Most treatment-related adverse events were mild or moderate, and serious adverse events were infrequent, with no clinically meaningful abnormal trend in laboratory parameters. CONCLUSIONS: Socrodeucitinib demonstrated significantly greater clearing of psoriasis plaques compared to placebo in patients with moderate-to-severe plaque psoriasis and illustrated a favourable safety and tolerability profile, warranting further investigation in longer-duration and larger trials.