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 end points were analyzed using multiple imputation.

Results
Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, 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). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and 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 vs placebo and a safety profile in line with PDE4 inhibition.