Generalized pustular psoriasis (GPP) patients who responded to AnaptysBio, Inc.’s investigational imsidolimab (IL-36R mAb) in GEMINI-1 and moved into GEMINI-2 maintained clear or almost clear skin through at Week 24, according to topline results reported by the Company.

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. Of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at Week 4.

Sixteen GPPPGA 0/1 responders 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. These 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 demonstrated 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

 “The results of these modestly sized studies reinforce that only one single IV dose of imsidolimab was required to achieve rapid clearance of GPP through four weeks and maintained in patients receiving a monthly SC maintenance dose,” says Daniel Faga, President and Chief Executive Officer of Anaptys, in a news release.

What’s Next for IL-36R mAb?

Anaptys plans to submit a data abstract for GEMINI-1 and GEMINI-2 results to a medical meeting later this year.

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.

“We’re immensely grateful to all the study investigators, study staff and trial participants who helped evaluate this potential new treatment option for GPP,” says Paul Lizzul, MD., PhD, chief medical officer of Anaptys. “We’re pleased that we have generated clinically meaningful data to support a potential future regulatory submission.”

PHOTO CREDIT: DermNet