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 at week 4. Participants could then roll over to GEMINI-2. 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 (53.4%) compared with placebo (13.3%; P=0.0131). 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).
“Regarding the safety and tolerability, treatment-emergent adverse events were similar in both groups,” Prof. Adam Reich (Medical College of Rzeszow, Poland) 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.
Medical writing support was provided by Karin Drooff MPH