The following is a summary of “Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS),” published in the March 2024 issue of Dermatology by Warren, et al.
Orismilast, a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor, is under investigation as a potential treatment for moderate-to-severe psoriasis. For a study, researchers sought to assess the efficacy and safety of orismilast modified-release formulation in patients with moderate-to-severe psoriasis.
A multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study was conducted in adults with moderate-to-severe plaque psoriasis. Efficacy endpoints were analyzed using multiple imputations.
Among 202 randomized patients, baseline characteristics were balanced across arms, except for a greater proportion of severe disease in the orismilast groups compared to placebo. Orismilast demonstrated significant improvements in the primary endpoint, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast –52.6% to –63.7% and placebo –17.3%; all P < .001). A greater proportion of patients receiving orismilast achieved PASI75 (39.5%-49.0%; P < .05) and PASI90 (22.0%-28.3%; P < .05 for 20 and 40 mg) compared to placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were consistent with PDE4 inhibition, with dose-dependent tolerability effects observed. Limitations of this study included small sample size, disease severity imbalance between groups, limited study duration, and diversity in the study population.
Orismilast demonstrated greater efficacy than placebo and exhibited a safety profile consistent with PDE4 inhibition.