Imsidolimab’s Biologics License Application for Treatment of GPP Submitted to FDA

Vanda Pharmaceuticals Inc. has announced its filing of a Biologics License Application (BLA) with the US Food and Drug Administration (FDA) seeking approval of imsidolimab for the treatment of generalized pustular psoriasis (GPP).1

GPP is an uncommon but severe autoinflammatory skin disease. The condition can be life-threatening and is characterized by abrupt episodes of significant skin redness, widespread sterile pustules, and systemic manifestations including fever and profound fatigue. GPP is largely linked to loss-of-function mutations in the interleukin (IL)-36RN gene, resulting in the impaired regulation of the IL-36 inflammatory pathway.2

"The submission of the BLA for imsidolimab marks a critical milestone in our efforts to bring this innovative therapy to patients suffering from GPP," said Mihael H. Polymeropoulos, MD, president, CEO, and Chairman of the Board of Vanda Pharmaceuticals, said in a statement.1

GPP was described in Vanda's release as an area of notable unmet medical need, with its reported rate of prevalence varying significantly across geographic areas.3 The disease's estimates ranging from roughly 2 to as high as 124 cases per million people around the world, with diminished rates generally observed in Europe and increased rates seen in regions of Asia.

The GPP drug itself, imsidolimab, is a fully human IgG4 antibody designed to suppress IL-36 receptor signaling, thereby compensating for the decreased activity of the endogenous IL-36 receptor antagonist that is commonly noted in individuals living with GPP due to IL36RN mutations. Development of this medication is being done specifically for this rare orphan indication.

Data on the efficacy of this medication which support the BLA come from the phase 3 GEMINI-1 trial. In this study, 45 patients were recruited for evaluation who were randomized in a 1:1:1 ratio to be treated with a single intravenous dose of 750 mg imsidolimab, 300 mg imsidolimab, or placebo on Day 0. By the 4-week mark, serving the investigators as the primary endpoint, 53% of patients treated with imsidolimab at either dose attained a Generalized Pustular Psoriasis Physician Global Assessment score of 0 or 1, suggesting clear or almost clear skin.

This was compared to only 13% of individuals included in the placebo cohort of the study. For those in the 750 mg dose group, the difference was statistically significant, with a P-value of .0131. Those who responded to treatment in GEMINI-1 were subsequently placed into the GEMINI-2 analysis, during which they were re-randomized to receive subcutaneous maintenance therapy each month with 200 mg imsidolimab or placebo. They were followed for as long as 116 weeks.

During the GEMINI-2 maintenance phase, all patients being given active imsidolimab maintained clear or nearly clear skin without reports of any GPP flares.1 Meanwhile, only 25% of those included in the placebo maintenance arm maintained response, and 63% experienced flares. Across both GEMINI analyses, imsidolimab was shown to have been generally well tolerated. The investigators did not identify any treatment-related serious adverse events reported and no discontinuations resulting from occurrence of adverse events.

Overall, the BLA submission is supported by consistent findings from the global GEMINI-1 and GEMINI-2 phase 3 studies, demonstrating that a single intravenous dose of imsidolimab may result in rapidly controlled disease activity among those with GPP. Additionally, the trials suggest clinical benefit can be sustained for nearly 2 years with monthly maintenance dosing.

Vanda has also requested priority review of the application, noting the serious nature of GPP and the lack of adequate therapies available for this rare orphan disease. Provided the FDA grants priority review, the agency would aim to complete its assessment within 6 months. This could allow for a potential approval of imsidolimab for GPP as early as mid-2026.

"Imsidolimab builds on our growing expertise in rare orphan disorders and our anti-inflammatory portfolio, including Ponvory®, which is approved for the treatment of relapsing forms of multiple sclerosis and is in clinical development for the treatment of psoriasis and ulcerative colitis," Polymeropoulos said in a statement.1 "We look forward to potential FDA approval and leveraging our commercial infrastructure to address this debilitating condition."

References

1. Vanda Announces Submission of Biologics License Application to the FDA for Imsidolimab for the Treatment of Generalized Pustular Psoriasis. Vanda Pharmaceuticals, Inc. December 15, 2025. https://www.prnewswire.com/news-releases/vanda-announces-submission-of-biologics-license-application-to-the-fda-for-imsidolimab-for-the-treatment-of-generalized-pustular-psoriasis-302641858.html.

2. Sachen KL, Arnold Greving CN, Towne JE. Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions. Cytokine 156, 155897 (2022).

3. Prinz JC, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. Journal of the European Academy of Dermatology and Venereology 37, 256–273 (2022).