TOPLINE:

Imsidolimab, a novel interleukin-36 receptor antagonist, significantly improved disease clearance at 4 weeks in patients with generalized pustular psoriasis (GPP), with no serious adverse events leading to treatment discontinuation through 104 weeks in two phase 3 trials.

METHODOLOGY:

• Researchers conducted two phase 3 trials, GEMINI-1 and GEMINI-2, in adults with moderate-to-severe GPP in 11 countries from October 2021 to August 2023.
• In GEMINI-1, 45 patients were randomly assigned in a 1:1:1 ratio to receive a single intravenous 300-mg dose of imsidolimab, a single intravenous 750-mg dose of imsidolimab, or placebo. The primary endpoint in GEMINI-1 was a GPP Physician Global Assessment scores of 0 (clear) or 1 (almost clear) at week 4.
• GEMINI-2 enrolled 42 patients from GEMINI-1 for long-term safety evaluation (up to 104 weeks), with responders (n = 16) randomly assigned in a 1:1 ratio to receive 200 mg of subcutaneous imsidolimab or placebo monthly. Partial responders (n = 12) received 200 mg of subcutaneous imsidolimab monthly. Of the patients who needed rescue therapy (n = 14) who received rescue therapy in GEMINI-1, nine received an intravenous imsidolimab dose of 750 mg followed by a 200 mg subcutaneous dose monthly, and five received “any” treatment to control intolerable GPP symptoms.
• The primary outcome for GEMINI-2 was long-term safety, with secondary endpoints including zero recurrence of GPP flares through week 24.

TAKEAWAY:

• In GEMINI-1, 53% of patients receiving either 300 mg or 750 mg of imsidolimab achieved “clear” or “almost clear” skin at week 4 compared with 13% of those on placebo (P = .02 for both comparisons).
• At week 1, 67% of those on the 300-mg dose and 40% of patients of those on the 750-mg dose, respectively, achieved a Pustulation Rating Scale score of 0 or 1 (no visible or very few pustules) compared with 13% of those receiving placebo.
• In GEMINI-2, all responders (100%) treated with 200 mg of subcutaneous imsidolimab had no recurrences of GPP flares through week 24 compared with 63% of responders treated with placebo (95% CI, 2.9-70.6).
• No deaths or serious adverse events leading to drug withdrawal were reported; infections were the most common treatment-emergent adverse event (which were low and similar to those on placebo); six patients in GEMINI-2 reported severe treatment-emergent adverse events; and seven had treatment-emergent antidrug antibodies (ADAs), including two with positive neutralizing ADAs.

IN PRACTICE:

“GEMINI-1 and GEMINI-2 demonstrated that a significantly higher proportion of patients with GPP randomly assigned to receive a single intravenous dose of imsidolimab compared with placebo were clear or almost clear of the disease after 4 weeks,” the authors of the study wrote, noting “no serious adverse events that led to treatment discontinuation with imsidolimab up to 104 weeks of treatment.”

SOURCE:

The study was led by Sandra Smieszek, PhD, Vanda Pharmaceuticals Inc., Washington, DC. It was published online on April 28 in NEJM Evidence.

LIMITATIONS: 

The limitations included a modest sample size and limited long-term placebo comparisons. 

DISCLOSURES:

AnaptysBio provided funding for the study, along with Vanda Pharmaceuticals. Many authors reported being employed by or owning stock in AnaptysBio and Vanda Pharmaceuticals (which acquired imsidolimab from AnaptysBio in 2025). Some authors also disclosed receiving consulting, investigator, and personal fees from several drug companies, including AnaptysBio and Vanda Pharmaceuticals.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.