AnaptysBio, Inc. announced positive top-line results from its global GEMINI-1 and GEMINI-2 Phase 3 trials evaluating the safety and efficacy of investigational imsidolimab (IL-36R mAb) in patients with generalized pustular psoriasis (GPP), a severe orphan disease that is potentially life-threatening if left untreated. In the 45-patient GEMINI-1 Phase 3 trial, patients were randomized 1:1:1 to receive a single infusion of 750mg intravenous (IV) imsidolimab, 300mg IV imsidolimab or placebo at Day 0. Of the patients who received a single dose of 750mg IV imsidolimab, 53% achieved a GPP Physician Global Assessment (GPPPGA) score of 0/1 (clear or almost clear skin) at Week 4 (primary endpoint), compared to 13% of the patients on placebo (p=0.0131). Of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at Week 4. Sixteen GPPPGA 0/1 responder patients from GEMINI-1 were subsequently re-randomized to monthly maintenance dosing of either 200mg subcutaneous (SC) imsidolimab or placebo in the GEMINI-2 Phase 3 trial.

Patients were followed for at least 24 weeks and up to a maximum of 92 weeks. Of the eight responding patients from GEMINI-1 who were re-randomized to monthly 200mg SC imsidolimab maintenance therapy, 100% maintained a GPPPGA score of 0/1 and none of them experienced a flare. Of the remaining eight responding patients from GEMINI-1 who were re-randomized to placebo, 25% maintained a GPPPGA score of 0/1 and 63% experienced a flare.

Data from both trials demonstrate a consistent, favorable safety and tolerability profile with no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported in imsidolimab-treated patients. Additionally, the data show: Low incidence and no elevation of infections versus placebo, No cases reported of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Guillain-Barre syndrome (GBS), No infusion reactions reported, Overall incidence of anti-drug antibodies (ADA) was low and, when detected, determined to be non-neutralizing. Anaptys plans to submit a comprehensive data abstract for GEMINI-1 and GEMINI-2 results to a H2 2024 medical meeting.

With all patients having passed 24 weeks and the furthest patient being treated through 92 weeks, the company is concluding the GEMINI-2 trial. The company plans to out-license imsidolimab in 2024, and a potential future filing of a biologics license application (BLA) with the U.S. Food and Drug Administration (FDA) will be contingent on an out-licensing transaction. Anaptys?

first Phase 3 GEMINI-1 clinical trial was a four week, double-blind, placebo-controlled, randomized study to evaluate the efficacy and safety of imsidolimab in patients with GPP, irrespective of mutational status. A total of 45 patients, 15 patients per arm, were enrolled across diverse global regions ranging from the U.S., EU, MENA, and Asia. Patients were randomized 1:1:1 to receive a single infusion of 750mg IV imsidolimab, 300mg IV imsidolimab or placebo at Day 0. The objective of the GEMINI-2 trial was to assess the safety and efficacy of imsidolimab for maintenance of response, and the prevention of GPP flares with monthly SC dosing.

A total of 42 patients were subsequently re-randomized into GEMINI-2. The 16 GPPPGA 0/1 responder patients from GEMINI-1 were re-randomized 1:1 to receive either monthly SC maintenance therapy of 200mg imsidolimab or placebo. Imsidolimab is a fully humanized IgG4 antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, that is being developed for the treatment of GPP. GPP is a rare, chronic, systemic autoinflammatory disease that is potentially life-threatening if left untreated.

During a GPP flare, individuals experience the sudden eruption of painful pustules. These pustules appear over large areas of the skin, accompanied by redness, severe itchiness, and dry, cracked or scaly skin. People with GPP may also experience more general symptoms such as fever, headache, extreme tiredness or a burning sensation on the skin.