Orismilast, a phosphodiesterase 4B/D inhibitor, in moderate-to-severe atopic dermatitis: efficacy and safety from a multicentre randomized placebo-controlled phase IIb dose-ranging study (ADESOS).

BACKGROUND

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic treatments with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase 4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

OBJECTIVES

To evaluate the optimal dose, efficacy and safety of twice-daily orismilast in patients with moderate-to-severe AD.

METHODS

This 16-week, multicentre randomized placebo-controlled phase IIb dose-ranging study (NCT05469464) included patients from 48 centres in Europe and the USA. Adults with moderate-to-severe AD were given (1 : 1 : 1 : 1) orismilast 20 mg, 30 mg or 40 mg, or placebo, twice daily. The primary endpoint was percentage change in Eczema Area and Severity Index (EASI); the secondary endpoints (all at week 16) included achievement of a score of clear (0) or almost clear (1) with ≥ 2-point improvement on the Investigator Global Assessment (IGA 0/1); achievement of a Peak Pruritus Numerical Rating Scale (PP-NRS) reduction of ≥ 4 points; and achievement of a reduction in EASI of 75%, 90% and 100% from baseline.

RESULTS

Overall, 233 patients were randomly assigned to orismilast 20 mg (n = 58), 30 mg (n = 61), 40 mg (n = 59) or placebo (n = 55). At week 16, reductions in EASI (percentage points) from baseline to week 16 were seen across orismilast groups and placebo (P > 0.05 for orismilast vs. placebo). Significantly more patients achieved IGA 0/1 with a ≥ 2-point improvement with orismilast 20 mg and 40 mg compared with placebo (P < 0.05). Significantly greater proportions of patients achieving a ≥ 4-point reduction in PP-NRS were demonstrated with orismilast at week 2. The safety profile was consistent with that of the PDE4 class, with no major safety concerns reported.

CONCLUSIONS

These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel oral therapy for the treatment of AD.