Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka Pharmaceutical Co., Ltd. plan to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for sibeprenlimab in the first half of 2025. This investigational drug aims to treat immunoglobulin A nephropathy (IgA nephropathy) in adults. This decision follows a positive interim analysis from the Phase 3 VISIONARY study and subsequent discussions with the FDA.
Sibeprenlimab, an anti-APRIL monoclonal antibody, targets a crucial step in the immune response that drives IgA nephropathy. It works by inhibiting A Proliferation-Inducing Ligand (APRIL), thus limiting the production of aberrant IgA1 (Gd-IgA1) and the formation of harmful immune complexes. IgA nephropathy is a progressive autoimmune disease affecting the kidneys. It often leads to end-stage kidney disease (ESKD). Previously, sibeprenlimab received Breakthrough Therapy designation based on promising results from the Phase 2 ENVISION clinical trial.
The ongoing Phase 3 VISIONARY study, which is blinded, will continue to monitor changes in kidney function, measured by estimated glomerular filtration rate (eGFR), until early 2026. Additional analyses of the collected data will be performed and shared to fully understand sibeprenlimab’s potential in treating this condition.
Developed and engineered by Visterra, Inc. (an Otsuka subsidiary), sibeprenlimab underwent pre-clinical and early-stage trials at Visterra. The drug’s mechanism of action centers on blocking APRIL, a critical factor in the four-hit pathogenic cascade of IgA nephropathy. APRIL sustains the disease’s progression by stimulating the production of Gd-IgA1 and immune complex formation. Sibeprenlimab’s neutralization of APRIL potentially reduces IgA and Gd-IgA1 levels. This reduction may lead to less auto-antibody production, fewer immune complexes deposited in the kidney, and decreased proteinuria and kidney inflammation. Ultimately, by reducing Gd-IgA1 production, sibeprenlimab aims to slow kidney damage and the progression toward ESKD. This targeted approach addresses a specific driver of nephron loss in IgA nephropathy.
IgA nephropathy, also known as Berger’s disease, primarily affects adults between 20 and 40 years old. Characterized by IgA accumulation in the kidneys, this chronic condition can lead to progressive kidney dysfunction and ultimately ESKD. Although supportive care exists for managing symptoms, ongoing research is vital for improving understanding and treatment options.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
