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.
Atopic dermatitis (‘AD’ for short) is also known as eczema. It is a common condition that causes red, itchy and inflamed skin. It also affects a person’s immune system. We aimed to find the best dose of a new medication called ‘orismilast’. We also wanted to check how well it works and how safe it is for adults with moderate-to-severe AD. For 16 weeks, people with AD were randomly given either 20, 30 or 40 milligrams of orismilast twice a day, or a placebo (a pill with no active medication). We measured how well the treatment worked by looking at the number of people whose skin cleared up or almost cleared up and how much itching was reduced. We used a measurement tool called the ‘EASI’ to monitor improvements. We also looked for side effects to check the medication’s safety. By week 16, more people who took 20 or 40 milligram doses of orismilast had clearer skin than those taking the placebo. People who took orismilast also reported less itching as early as week 2. Improvements in EASI score were seen across all the groups, including those taking placebo. The side effects were similar to those seen with other similar medications. Studies that divide patients into smaller groups to test different doses can lead to variation. This must be considered when assessing how well different doses of a medication work and which doses should be taken into the next trials. We suggest that orismilast could be a promising new treatment for people with AD.
© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.