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)

Background Orismilast is a novel oral phosphodiesterase 4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. Objective To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. Methods This 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 evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy endpoints were analyzed using multiple imputation. Results Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast versus placebo. Orismilast showed 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%; placebo, –17.3%; all P<0.001). Greater proportions receiving orismilast achieved PASI75 (39.5% to 49.0%; P<0.05) and PASI90 (22.0% to 28.3%; P<0.05 for 20 and 40 mg) versus placebo (PASI75, 16.5%; PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. Limitations Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. Conclusion Orismilast demonstrated greater efficacy versus placebo and a safety profile in line with PDE4 inhibition.