Imsidolimab potential future therapeutic avenue for generalised pustular psoriasis

The phase 3 GEMINI-1 and -2 trials demonstrated the efficacy of imsidolimab in treating generalised pustular psoriasis (GPP), with over half of the participants achieving clear or almost clear skin in the Generalised Pustular Psoriasis Physician Global Assessment (GPPPGA) score within 4 weeks after a single 750 mg dose. Subsequent subcutaneous maintenance therapy significantly reduced the occurrence of GPP flares.

“GPP is a rare, severe systemic inflammatory disease and it can be really debilitating, often life-threatening. Based on our current knowledge, its pathogenesis is attributed to the abnormal activity of IL-36,” Prof. Adam Reich (University of Rzeszów, Poland) explained [1]. The phase 3 GEMINI-1 and -2 trials (NCT05352893 and NCT05366855) assessed the IL-36 receptor antibody imsidolimab in GPP.

In GEMINI-1, 45 adult participants with moderate-to-severe GPP flare were randomised to a single dose of intravenous imsidolimab at 750 mg, 300 mg, or placebo with a primary endpoint of GPPPGA score 0/1, corresponding to clear or almost clear skin regarding erythema, pustules, and scaling at week 4. Participants could then roll over to GEMINI-2, where responders were re-randomised to subcutaneous imsidolimab maintenance 200 mg every 4 weeks or placebo, while non-responders with prior placebo received a high dose of intravenous imsidolimab followed by 200 mg subcutaneous.

At week 4, significantly more participants achieved the primary endpoint of GPPPGA 0/1 with 1 dose of 750 mg imsidolimab compared with placebo (53.4% vs 13.3%; P=0.0131; see Figure). The response rate for 300 mg was 53.3%. As for flare prevention over at least 24 weeks, assessed in GEMINI-2, all participants on imsidolimab maintained GPPPGA 0/1 without flaring. On placebo, 25% sustained GPPPGA 0/1 and 62.5% experienced a flare. Statistical significance for the difference was irrespective of an initial single dosage before maintenance (750 mg intravenous/200 mg subcutaneous vs placebo, P=0.0145; 300 mg intravenous/200 mg subcutaneous, P=0.0121).

Figure: Proportion of participants achieving a Generalised Pustular Psoriasis Physician Global Assessment (GPPPGA) 0/1 over time [1]



“Regarding the safety and tolerability, treatment-emergent adverse events were similar in both groups,” Prof. Reich announced, adding that no serious adverse events led to treatment discontinuation and the incidence of infection was low. “We may say that imsidolimab represents a promising therapeutic option for patients with moderate-to-severe GPP,” Prof. Reich concluded.

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   1. Reich A, et al. Imsidolimab, an IL-36 receptor antagonist, was effective and well tolerated for treatment and prevention of flares in patients with generalised pustular psoriasis: results from the phase 3 trials, GEMINI-1 and GEMINI-2. EPS06.05, EADV Congress 2024, 25–28 September, Amsterdam, the Netherlands.

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Posted on 6 November 20246 November 2024