GEMINI-1 and GEMINI-2 phase III: Imsidolimab for GPP

Results from the randomized, double-blind, placebo-controlled, phase III GEMINI-1 (NCT05352893) trial and the follow-on phase III GEMINI-2 (NCT05366855) relapse-prevention extension trial, investigating imsidolimab, a humanized immunoglobulin G4 monoclonal antibody targeting the interleukin-36 (IL-36) receptor, in adults with generalized pustular psoriasis (GPP) were published in NEJM Evidence by Smieszek et al. The primary endpoint of GEMINI-1 (N = 45) was the proportion of patients achieving a GPP Physician Global Assessment (GPPPGA) score of 0 or 1 at Week 4. The primary objective of GEMINI-2 (N = 42) was to evaluate the long-term safety of imsidolimab in patients enrolled in GEMINI-1. 

Key data: In GEMINI-1, 53% of study participants receiving either 300 mg or 750 mg intravenous (IV) imsidolimab achieved a GPPPGA score of 0 or 1 at Week 4 vs 13% receiving placebo, with a risk difference of 40 percentage points for both dose groups (95% confidence interval [CI], 9–71; p = 0.02). In GEMINI-2, no serious adverse events (SAEs) led to imsidolimab discontinuation over up to 104 weeks. All patients receiving 200 mg subcutaneous (SC) imsidolimab monthly had zero recurrence of GPP flare through Week 24 vs 63% receiving placebo, with a risk difference of 37 percentage points (95% CI, 2.9–70.6). 

Key learning: A single IV dose of imsidolimab demonstrated a significant improvement in GPPPGA response rates at Week 4 in adults with GPP, with no SAEs leading to treatment discontinuation over up to 104 weeks. The small sample size, reflecting the rarity of GPP, represents a key limitation of the GEMINI trials.