New top-line data from a global Phase 3 clinical trial of patients with generalized pustular psoriasis (GPP) flares show rapid clearance of pustulation, erythema and scaling through four weeks after a single dose of 750 mg intravenous (IV) imsidolimab. Imsidolimab is a humanized IgG4 monoclonal antibody that inhibits the function of the interleukin-36 receptor (IL-36R mAb), a signaling pathway within the immune system shown to be involved in the pathogenesis of inflammatory diseases, including GPP.
More than half of patients (53.3 percent) who received a single dose of 750 mg IV imsidolimab achieved clear or almost clear skin (Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) 0/1) by four weeks after dosing, compared to 13.3% of patients on placebo (p=0.0131).
Additionally, imsidolimab was well tolerated with no imsidolimab-related serious adverse events (AEs) or severe AEs reported through end of study. All AEs reported in imsidolimab-treated patients were mild or moderate and balanced across imsidolimab-treated vs. placebo patients, including a low incidence and no elevation of infections. Only one of 30 (3.3%) imsidolimab-treated patients had detectable anti-drug antibodies (ADA), which were non-neutralizing.
“GPP is an unpredictable and potentially life-threatening skin disease with systemic symptoms,” said Professor Hervé Bachelez, M.D., Ph.D., Hôpital Saint-Louis, Paris, one of the world’s leading experts on GPP. “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.”
GPP is a rare but debilitating skin disease that can be life-threatening if left untreated. It develops when a person’s immune system is over-activated, which leads to inflammation. People living with GPP experience flares of swollen and often painful pustules, or blister-like sores, on their skin. While the severity of symptoms that people with GPP experience differs, the negative impact on quality of life is universal. Patients often wait years for an accurate diagnosis and even after they’re finally diagnosed, they continue to experience poor control of symptoms while on current treatment options.1
Understanding the pathophysiology of GPP and the role of the IL-36 pathway
Targeting the IL-36 pathway has become of particular interest since its role as an underlying biological driver of GPP was discovered.2 IL-36 receptor (IL-36r) is a protein that helps to regulate, or turn on, the pathway. There are several different IL-36 proteins that work in harmony to ensure a balanced immune response.3
When the IL-36 pathway is stimulated or turned on, there is an increase in IL-36r signaling, causing inflammation. Skin cells known as keratinocytes grow and release proteins that attract white blood cells, which makes inflammation worse. This is the reason why people with GPP develop pustules on their skin.4
New top-line data from first study to use novel assessment of GPP severity
The registration-enabling GEMINI-1 Phase 3 trial for imsidolimab is the first randomized, double-blind, placebo-controlled trial to use the composite endpoint of 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.
A total of 45 patients, 15 patients per arm, were enrolled across diverse global regions. Patients were randomized 1:1:1 to receive a single infusion of 750 mg IV imsidolimab, 300 mg IV imsidolimab or placebo at Day 0.
Additionally, 66.7% (10/15) of placebo patients exited GEMINI-1 early, crossed-over to GEMINI-2 and were eligible to receive rescue therapy with a single dose of 750 mg IV imsidolimab.
AnaptysBio, Inc., the company developing imsidolimab, plans to present comprehensive data from GEMINI-1 and top-line GEMINI-2 results at a medical meeting in H2 2024. Additionally, AnaptysBio anticipates filing a biologics license application (BLA) with the U.S. Food and Drug Administration by the third quarter of 2024.
AnaptysBio intends to out-license imsidolimab in 2024 and reallocate the potential proceeds of a transaction to further invest in the broad development of its best-in-class immune cell modulators in autoimmune and inflammatory diseases. To find out more, visit them here.
2 Sugiura K. Role of Interleukin 36 in Generalised Pustular Psoriasis and Beyond. Dermatol. Ther. (Heidelb). 2022; 12(2): 315-328.
3 Boutet M-A, Bart G, Penhoat M, Amiaud J, et al. Distinct expression of interleukin (IL)‐36α, β and γ, their antagonist IL‐36Ra and IL‐38 in psoriasis, rheumatoid arthritis and Crohn's disease. Clin. Exp. Immunol. 2016; 184(2): 159-173. doi: 10.1111/cei.12761
4 Queen D, Ediriweera C and Liang L. Function and Regulation of IL-36 Signaling in Inflammatory Diseases and Cancer Development. Front. Cell Dev. Biol. 2019; 7: 317. doi: 10.3389/fcell.2019.00317