Targeting IL-36 signaling, imsidolimab significantly increased clear or almost clear skin responses at Week 4 compared with placebo, with sustained improvements observed through 24 weeks during monthly subcutaneous maintenance treatment.
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Imsidolimab demonstrated significantly higher rates of clinical clearance than placebo in patients experiencing a generalized pustular psoriasis (GPP) flare, according to phase 3 data published in NEJM Evidence.1
GPP is a rare, potentially life-threatening inflammatory skin disease characterized by recurrent flares of widespread sterile pustules, erythema, and systemic symptoms.2 Aberrant IL-36 activity, often associated with variants in the IL-36 receptor antagonist gene, has been implicated in disease pathogenesis.3 Imsidolimab is a humanized, affinity-matured immunoglobulin G4 monoclonal antibody designed to bind the IL-36 receptor and inhibit IL-36 signaling.4
The publication reported findings from two phase 3 trials conducted across 26 clinical sites in 11 countries.1 GEMINI-1 (NCT05352893) was a double-blind, placebo-controlled trial that enrolled 45 adults aged 18–80 years experiencing a GPP flare. Participants were randomly assigned to receive a single intravenous dose of imsidolimab 300 mg, imsidolimab 750 mg, or placebo over approximately 60 minutes. The primary endpoint was achievement of a Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) score of clear or almost clear at Week 4.
At Week 4, 53% of patients in both imsidolimab groups achieved clear or almost clear disease, compared with 13% of patients receiving placebo. This difference was statistically significant for both the 300 mg and 750 mg doses compared with placebo (p=0.023).1
GEMINI-2 (NCT05366855) was a follow-on relapse prevention study that primarily evaluated longer-term safety for up to 104 weeks. Patients who improved in GEMINI-1 were randomized to monthly subcutaneous imsidolimab 200 mg or placebo, while partial responders received open-label monthly imsidolimab. No serious adverse events led to imsidolimab discontinuation during GEMINI-2, and no cases of drug reaction with eosinophilia, Guillain–Barré syndrome, or other severe immune-mediated disorders were reported in either study. Exploratory immunogenicity evaluations reported one patient (3%) with treatment-boosted antidrug antibodies in GEMINI-1 and seven patients (17%) with treatment-emergent antidrug antibodies in GEMINI-2.1
Treatment options for GPP remain limited. These findings add further evidence supporting IL-36 receptor blockade as a targeted approach for GPP. The randomized trials included a small number of patients, reflecting the rarity of GPP; despite this, the sample size was adequate to demonstrate significant improvement in the primary efficacy outcome in GEMINI-1.1
References
- Smieszek S, Przychodzen B, Tyner C, et al. Efficacy and safety of imsidolimab for generalized pustular psoriasis. NEJM Evid. 2026;5(5). doi: 10.1056/EVIDoa2500272.
- Choon SE, van der Kerkhof P, Gudjonsson JE, et al. International consensus definition and diagnostic criteria for generalized pustular psoriasis from the International Psoriasis Council. JAMA Dermatol. 2024;160:758.
- Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–8.
- Warren RB, et al. Imsidolimab, an anti-interleukin-36 receptor monoclonal antibody, for the treatment of generalized pustular psoriasis: results from the phase 2 GALLOP trial. Br J Dermatol. 2023;189:161–9.
Disclosure: This article was created by the touchDERMATOLOGY team utilizing AI as an editorial tool (ChatGPT [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: Imsidolimab improves clinical clearance in phase 3 generalized pustular psoriasis trial. TouchDERMATOLOGY. 11 June 2026
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