Orismilast demonstrates efficacy, early itch reduction in atopic dermatitis
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Key takeaways:
- Orismilast 40 mg group achieved the best results with 31% of patients reaching IGA 0 or 1 by week 16.
- IGA 0 or 1 was also achieved by 26% and 30 mg of the orismilast 20 mg and 30 mg groups, respectively.
Orismilast outperformed placebo in the treatment of moderate to severe atopic dermatitis in adults, according to a poster presented at the European Academy of Dermatology and Venereology Congress.
“Orismilast is a potent, selective phosphodiesterase 4 (PDE4)-B and -D inhibitor, which showed significant efficacy in a phase 2b psoriasis study,” Eric L. Simpson, MD, MCR, Frances J. Storrs Medical Dermatology Professor at Oregon Health & Science University, and colleagues wrote in the poster. “PDE4-B and PDE4-D isoforms are over-expressed in the skin of patients with atopic dermatitis, compared to healthy individuals.”
As a result, the authors conducted the phase 2b, double-blinded, placebo-controlled ADESOS study where they assessed the efficacy and safety of orismilast for the treatment of moderate to severe AD in adults.
Patients were randomly assigned to receive orismilast 20 mg (n = 58), 30 mg (n = 61), 40 mg (n = 59) or placebo (n = 55) twice daily for 16 weeks.
Results showed that the orismilast 40 mg group achieved the best results with 31% of patients reaching IGA 0 or 1 by week 16. This was followed by the orismilast 20 mg group at 26%, the orismilast 30 mg group at 24% and the placebo group at 10%.
Similarly, 60%, 50% and 57% of patients treated with 40 mg, 30 mg and 20 mg of orismilast, respectively, reached a 4-point or more reduction in peak pruritus NRS by week 16 vs. 42% of placebo.
In the same time frame, EASI 75 was also achieved by 36%, 26% and 30% of the 40 mg, 30 mg and 20 mg groups, respectively; however, 36% of the placebo group also reached EASI 75.
“The study was impacted by a high EASI placebo rate; however, in severe patients, the 20 mg dose separated from placebo for EASI 75 and EASI 90 measurements, consistent with the overall findings as measured by IGA 0/1, patient-reported efficacy and objective biomarkers,” the authors wrote.
Additionally, the percentage decreased to 0% in the placebo group when looking at EASI 100, whereas the orismilast group still maintained a response of 5% to 8%.
Treatment-emergent adverse events were experienced by 75.9% to 86.4% of orismilast-treated patients, a trend which appeared to be dose-dependent, vs. 63.6% in the placebo group. Two serious treatment-emergent adverse events occurred in the treatment group, one being in the 20 mg group and the other in the 40 mg group.
“These data confirm the clinical relevance of high potency PDE4B/D selective inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD and other inflammatory diseases,” the authors wrote.