- Simpson E, et al. Orismilast efficacy in adults with moderate-to-severe atopic dermatitis in a phase 2b trial: early impact on itch and patient-reported outcomes. D1T01.1C, EADV Congress 2024, 25–28 September, Amsterdam, the Netherlands.
In the phase 2b, dose-ranging ADESOS trial, Prof. Eric Simpson (Oregon Health and Science University, OR, USA) and colleagues randomised 233 adults with moderate-to-severe AD to placebo or one of the orismilast arms at dosages of twice daily 20 mg, 30 mg, or 40 mg for 16 weeks1.
The 4 study arms were overall balanced at baseline. The cohort included 51% women, and the mean age was 37.0. Of note, the mean Eczema Area and Severity Index (EASI) score was 22.7, 15% of the participants had an IGA indicating severe disease.
At week 16, all dosages of orismilast showed significantly higher rates of IGA 0/1 than placebo in the primary analysis: 26% (20 mg), 24% (30 mg), 31% (40 mg), compared with 10% on placebo (all P<0.05). The picture was not so clear for EASI response. For example, EASI75 response rates were 36% in the placebo arm and 30%, 26%, and 36% in the orismilast arms. “We think it's probably an investigator training issue, because of that variability in EASI score,” Prof. Simpson stated. Looking at the subgroup with severe AD in the 20 mg arm, EASI75 and EASI90 rates were 31% and 12% compared with 21% and 6% on placebo, respectively.
The data for achieving a ≥4-point reduction in the Peak Pruritus Numerical Rating Scale (NRS) started to be significant at week 1 (8% placebo vs 21%, 25%, 32% on orismilast; P<0.05 for all comparisons), which increased to 10% placebo versus 30%, 33%, 34% at week 2. The ≥4-point Skin Pain NRS reduction rates were also statistically significant as of week 1.
No new safety signals were identified. The adverse events known in PDE-4 inhibition like diarrhoea and nausea mainly appeared within the first 4 weeks. In total, 2 serious adverse events occurred on orismilast. “I do feel like these data confirm the relevance of this approach in AD, and we're currently planning phase 3 studies,” Prof. Simpson concluded.
Medical writing support was provided by Karin Drooff MPH