Imsidolimab in Generalized Pustular Psoriasis: Efficacy and Safety

Key Takeaways

• Week 4 clear or almost clear status was reported more often with imsidolimab than with placebo.
• The phase 3 program included an initial efficacy trial followed by a relapse-prevention study.
• Across 104 weeks of follow-up, no serious adverse events led to imsidolimab discontinuation.

According to an NEJM Evidence report, imsidolimab showed an early signal in generalized pustular psoriasis, with 53% of patients in each active-dose group reaching clear or almost clear status at week 4. The study evaluated two phase 3 trials in this rare inflammatory disorder.

The two phase 3 trials were conducted at 26 clinical sites in 11 countries. GEMINI-1 enrolled 45 patients aged 18 to 80 years during a generalized pustular psoriasis flare. Patients were assigned equally to single intravenous imsidolimab 300 mg, single intravenous imsidolimab 750 mg, or placebo, with 15 patients in each group. The primary endpoint was a GPPPGA score of clear, or 0, or almost clear, or 1, at week 4. Imsidolimab is a humanized, affinity-matured IgG4 monoclonal antibody that binds the IL-36 receptor and blocks IL-36 signaling.

In GEMINI-1, 8 of 15 patients in each imsidolimab arm, or 53%, met the week 4 endpoint, compared with 2 of 15 patients, or 13%, in the placebo group. Both dose-versus-placebo comparisons were reported with P=0.023.

GEMINI-2 was the follow-on relapse-prevention trial, with a primary objective of evaluating imsidolimab safety through 104 weeks. Patients who improved in GEMINI-1 were randomized to monthly 200 mg subcutaneous imsidolimab or placebo. Partial responders received open-label monthly 200 mg subcutaneous imsidolimab. No serious adverse events led to imsidolimab discontinuation during the follow-on study.