Zasocitinib Effective in Moderate to Severe Psoriasis: Analysis

Key Takeaways

• Zasocitinib at 5 mg or higher achieved PASI 75 improvement in up to 68% of patients
• PASI 100 was acheived by 33% in the 30-mg group, with rapid response as early as 4 weeks
• Treatment-emergent adverse events were manageable and similar to placebo

Results from a recent placebo-controlled trial of zasocitinib showed promise in improving skin clearance for patients with moderate to severe plaque psoriasis.

The  phase 2b study, conducted across multiple centers in the United States and Canada, included 259 patients treated over 12 weeks. Participants received zasocitinib at doses of 2, 5, 15, or 30 mg daily or placebo. The primary endpoint was the acheivement of 75% improvement in Psoriasis Area and Severity Index (PASI 75) at 12 weeks, was met by 44% and 68% of patients in the 5-mg and 15-mg zasocitinib groups, respectively (vs. 6% in the placebo). Efficacy responses were dose-dependent up to 15 mg and the authors reported little difference between the 15-mg and 30-mg doses. PASI 100 scores (complete skin clearance) were achieved by 10%, 15%, and 33% of patients at the 5-, 15-, and 30-mg doses, respectively (no placebo patients achieved PASI 100).

Safety data showed a higher incidence of treatment-emergent adverse events (TEAEs) in the zasocitinib groups vs. placebo (53-62% vs. 44%), with common TEAEs including acne, diarrhea, and COVID-19. Discontinuations due to adverse events were minimal. The authors reported no major adverse cardiovascular events or thromboembolic events.

"In this randomized clinical trial, zasocitinib, an advanced, potent, and highly selective oral TYK2 inhibitor bioengineered to optimize target coverage and functional selectivity, achieved biologic-level efficacy with complete skin clearance observed after only a 12-week treatment period in up to one-third of patients, with a low incidence of known tolerability issues and absence of serious toxic effects that are characteristic of JAK1-3 inhibition,"  Two phase 3 studies of longer duration and with larger populations have been initiated to confirm these early observations."

Source: Armstrong A, et al. JAMA Dermatology. 2024. Doi:10.1001/jamadermatol.2024.2701