Anaptys Announces Positive Phase 3 Results for Imsidolimab in GPP

AnaptysBio, Inc., a clinical-stage biotechnology firm, has revealed promising top-line outcomes from its Phase 3 GEMINI-1 and GEMINI-2 trials, which assess the safety and effectiveness of the investigational drug imsidolimab (IL-36R mAb) in treating generalized pustular psoriasis (GPP). GPP is a severe, life-threatening orphan disease if not treated.

The GEMINI-1 trial included 45 patients who were randomly assigned to receive either a 750mg IV dose of imsidolimab, a 300mg IV dose of imsidolimab, or a placebo. Results showed that 53% of patients receiving the 750mg dose achieved a GPP Physician Global Assessment (GPPPGA) score indicating clear or almost clear skin at Week 4, compared to only 13% for those on placebo, with statistical significance (p=0.0131). Similarly, 53% of patients receiving the 300mg dose also achieved the same GPPPGA score at Week 4.

Following the GEMINI-1 trial, 16 patients who achieved a GPPPGA score of 0/1 were re-randomized in GEMINI-2 to receive monthly maintenance doses of either 200mg SC imsidolimab or a placebo. Over a follow-up period of at least 24 weeks and extending up to 92 weeks, all eight patients receiving the 200mg SC imsidolimab maintained clear to almost clear skin without experiencing a flare. In contrast, only 25% of the patients re-randomized to placebo maintained clear skin, and 63% experienced a flare.

Daniel Faga, the president and CEO of Anaptys, noted the significance of these trials in highlighting the company's capability to develop antibodies that yield meaningful outcomes for patients. He emphasized that even a single IV dose of imsidolimab could achieve rapid clearance of GPP, which could be maintained with monthly SC maintenance doses.

The safety and tolerability data from both GEMINI-1 and GEMINI-2 were favorable, with no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported among patients treated with imsidolimab. The trials also revealed a low incidence of infections without elevation compared to placebo, no cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Guillain-Barre syndrome (GBS), or infusion reactions, and a low overall incidence of anti-drug antibodies (ADA), which were non-neutralizing when detected.

AnaptysBio plans to submit a comprehensive data abstract summarizing the results of the GEMINI-1 and GEMINI-2 trials to a medical meeting in the second half of 2024. Following the conclusion of the GEMINI-2 trial, which has seen patients treated for up to 92 weeks, the company intends to out-license imsidolimab in 2024. A potential future filing of a biologics license application (BLA) with the U.S. Food and Drug Administration (FDA) will depend on successful out-licensing.

Paul Lizzul, M.D., Ph.D., the chief medical officer of Anaptys, expressed gratitude to all those involved in the trials and highlighted the generation of clinically meaningful data supporting a potential future regulatory submission for imsidolimab.

The GEMINI-1 trial was a four-week, double-blind, placebo-controlled, randomized study involving 45 patients from various global regions. The objective of the GEMINI-2 trial was to evaluate the safety and efficacy of imsidolimab for maintaining response and preventing GPP flares with monthly SC dosing. A total of 42 patients were re-randomized into GEMINI-2.

Imsidolimab is a fully humanized IgG4 antibody that inhibits the interleukin-36-receptor (IL-36R) and is being developed for treating GPP. GPP is a rare, chronic, systemic autoinflammatory disease causing painful pustules, redness, severe itching, and systemic symptoms such as fever and extreme tiredness.