Imsidolimab is an IgG4 antibody that inhibits the function of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of inflammatory diseases, including GPP.

AnaptysBio, Inc.’s Imsidolimab (IL-36R) performed well in in Generalized Pustular Psoriasis (GPP), according to topline results from the Phase 3 GEMINI-1 trial.

Imsidolimab is an IgG4 antibody that inhibits the function of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogenesis of inflammatory diseases, including GPP.

Imsidolimab met its primary endpoint in the study population achieving rapid clearance of pustulation, erythema and scaling through Week 4 after a single dose of 750mg IV imsidolimab. Anaptys plans to present comprehensive data from the study at a medical meeting in 2024. Furthermore, the company anticipates filing a biologics license application (BLA) with the U.S. Food and Drug Administration (FDA) by Q3 2024.

The registration-enabling GEMINI-1 trial in GPP, which recruited 45 patients, is the first randomized, double-blind, placebo-controlled trial to use the composite endpoint of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) at Week 4 as its primary assessment. The GPPPGA assessment, representing a stringent and comprehensive characterization of disease severity, required satisfying an overall clinical response score of 0/1 (clear or almost clear) collectively across each GPP disease attribute, including pustulation, erythema and scaling.

“GPP is an unpredictable and potentially life-threatening skin disease with systemic symptoms,” says Professor Hervé Bachelez, M.D., Ph.D., Hôpital Saint-Louis, Paris, in a news release.“Achieving positive top-line results utilizing the GPPPGA composite endpoint in this well conducted, randomized controlled, global trial, along with a compelling safety profile, represents the potential for a single dose of imsidolimab to predictably provide relief for patients living with this burdensome disease.”

Imsidolimab Met Primary Endpoint Achieving Rapid Clearance of GPP Through Week 4 After a Single Dose

Fully 53.3% of patients who received a single dose of 750mg IV imsidolimab achieved GPPPGA 0/1 (clear or almost clear) at Week 4 (primary endpoint), compared to 13.3% of patients on placebo.

Additionally, 66.7% of placebo patients exited GEMINI-1 early, crossed-over to GEMINI-2 and were eligible to receive rescue therapy with a single dose of 750mg IV imsidolimab.

Top-line data also demonstrate a favorable safety and tolerability profile . All adverse events reported in imsidolimab-treated patients were mild or moderate and balanced across imsidolimab-treated vs. placebo patients. There were no severe adverse events reported in imsidolimab-treated patients. In addition, there were no cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Guillain-Barre syndrome (GBS) reported. There was also a low incidence and no elevation of infections vs. placebo and no infusion reactions.  One of 30 (3.3%) imsidolimab-treated patients had detectable anti-drug antibodies, which were non-neutralizing.

Patients who were rescued or completed the GEMINI-1 trial are subsequently being enrolled in GEMINI-2, the second Phase 3 trial for imsidolimab in GPP, where they are receiving monthly doses of 200mg subcutaneous imsidolimab or placebo depending upon whether they are responders, partial responders or non-responders to treatment under GEMINI-1.

The objective of the ongoing GEMINI-2 trial is to assess the efficacy and safety of imsidolimab for the prevention and/or reduction in severity of recurrent GPP flares when dosed chronically as a monthly subcutaneous dosing over a three-year period.

“The success of the GEMINI-1 trial highlights Anaptys’ commitment to patients and our ability to internally discover and develop differentiated antibodies,” says Daniel Faga, president and chief executive officer of Anaptys, in a news release. “Moving forward, we intend to out-license imsidolimab with this compelling and competitive dataset to bring this therapy to patients living with this highly morbid condition and reallocate the potential proceeds of a transaction to further invest in the broad development of our best-in-class immune cell modulators, including our checkpoint agonists, in autoimmune and inflammatory diseases.”