AnaptysBio Announces Positive Topline Results from Phase 3 Trial of Imsidolimab for GPP

Generalized pustular psoriasis

Image credit: © DermNet

AnaptysBio recently announced new positive topline results from its global GEMINI-1 and GEMINI-2 phase 3 clinical trials evaluating the safety and efficacy of investigational imsidolimab (IL-36R mAb) in patients with generalized pustular psoriasis (GPP).¹

In GEMINI-1, 45 patients were randomized 1:1:1 to receive a single infusion of 750mg intravenous (IV) imsidolimab, 300mg IV imsidolimab, or placebo at day 0. Out 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, the primary end point of the study, compared to 13% of patients who received placebo (p=0.0131). Additionally, out of the patients who received a single dose of 300mg IV imsidolimab, 53% achieved GPPPGA 0/1 at week 4.

Overall, 16 patients who achieved GPPPGA 0/1 in GEMINI-1 were re-randomized to monthly maintenance dosing of either 200mg subcutaneous (SC) imsidolimab or placebo in GEMINI-2. Patients were monitored for at least 24 weeks and for up to a maximum of 92 weeks.

Out of the 8 patients who achieved GPPPGA 0/1 in GEMINI-1 who were re-randomized to receive monthly 200mg SC imsidolimab maintenance therapy, 100% maintained a GPPPGA score of 0/1 and no patients experienced a GPP flare. From the remaining 8 patients who achieved GPPPGA 0/1 in GEMINI-1 who were re-randomized to receive placebo, 25% maintained a GPPPGA score of 0/1 and 63% experienced a GPP flare.

"GPP is one of the many important deadly diseases we treat as dermatologists. It is also an exciting time for research as we are now better understanding the pathophysiology of GPP, which in turn leads to better treatments. The positive results from the imsidolimab study provides additional hope that another approved treatment option for GPP may become available to help our patients," said Dermatology Times' Spring Editor in Chief, Aaron Farberg, MD, FAAD, a double board-certified dermatologist, Mohs surgeon, and the chief medical officer of Bare Dermatology in Houston, Texas, in a statement.

Imsidolimab was well-tolerated in both GEMINI-1 and GEMINI-2 and there were no treatment-related serious adverse events (SAEs) or SAEs leading to discontinuation reported in patients treated with imsidolimab. In both trials, there was a low incidence and no elevation of infections compared to placebo, no reported cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Guillain-Barre syndrome (GBS), no reported infusion reactions, and the overall incidence of anti-drug antibodies was low.

“The success of the GEMINI-1 and GEMINI-2 phase 3 trials highlights Anaptys’ ability to internally discover and develop differentiated antibodies that deliver meaningful outcomes for patients. 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. We remain intent on out-licensing imsidolimab to bring this therapy to patients living with this highly morbid condition,” said Daniel Faga, president and chief executive officer of AnaptysBio, in the news release.

Now that GEMINI-2 is concluded, AnaptysBio stated that it plans to out-license imsidolimab in 2024. Additionally, AnaptysBio hopes to submit a Biologics License Application to the US Food and Drug Administration, contingent on the out-licensing agreement.

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

In October 2023, AnaptysBio first announced positive topline results from GEMINI-1, which included the primary end point of patients achieving rapid clearance of pustulation, erythema, and scaling through week 4 after a single dose of 750mg IV imsidolimab. Additionally, 66.7% (10/15) of patients who received placebo and who left GEMINI-1 early were moved to GEMINI-2 and were eligible to receive rescue therapy with a single dose of 750mg IV imsidolimab.²

References

1. Anaptys announces positive top-line GEMINI-2 phase 3 clinical trial results of imsidolimab (IL-36R) in generalized pustular psoriasis (GPP). News release. AnaptysBio. May 9, 2024. Accessed May 9, 2024. https://ir.anaptysbio.com/news-releases/news-release-details/anaptys-announces-positive-top-line-gemini-2-phase-3-clinical
2. Anaptys announces positive top-line phase 3 clinical trial results of imsidolimab (IL-36R) in generalized pustular psoriasis (GPP). News release. AnaptysBio. October 9, 2023. Accessed May 9, 2024. https://ir.anaptysbio.com/news-releases/news-release-details/anaptys-announces-positive-top-line-phase-3-clinical-trial