FDA Grants Priority Review to Otsuka's BLA for Sibeprenlimab in IgAN Treatment

PRINCETON, NJ, USA & TOKYO, Japan I May 27, 2025 I Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. have announced that the U.S. Food and Drug Administration (FDA) has accepted their Biologics License Application (BLA) for sibeprenlimab, a monoclonal antibody under investigation for its ability to inhibit APRIL (A Proliferation-Inducing Ligand) in adults suffering from immunoglobulin A nephropathy (IgAN). The disease, IgAN, involves the formation of autoantibodies against galactose-deficient IgA, immune complexes, and their deposition in the kidneys. Sibeprenlimab is presented as a single-dose, prefilled syringe intended for self-administration every four weeks, allowing patients the advantage of treatment in the comfort of their homes.

The application is supported by data from the Phase 3 VISIONARY clinical trial (NCT05248646), which achieved its primary endpoint during the interim analysis, and findings from the Phase 2 ENVISION clinical trial (NCT04287985). The clinical trials demonstrated that sibeprenlimab significantly reduced 24-hour proteinuria compared to placebo after nine months, indicating both statistical and clinical significance. The FDA has granted the BLA priority review status, with a Prescription Drug User Fee Act (PDUFA) target action date set for November 28, 2025.

John Kraus, M.D., Ph.D., the executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc., expressed that over the past decade, Otsuka has consistently pursued innovative solutions in nephrology to provide advancements for patients with complex conditions like IgA nephropathy. If approved, sibeprenlimab would offer patients the convenience of self-administering treatment every four weeks—potentially providing significant clinical benefits and ease to those affected by this disease.

Sibeprenlimab has been awarded Breakthrough Therapy designation for treating IgAN, based on positive results from the Phase 2 ENVISION trial. IgAN is a chronic autoimmune kidney disease that often progresses to end-stage kidney disease (ESKD) despite current optimized care. Targeting the APRIL protein offers a promising therapeutic approach to interfering with the pathogenesis of IgAN, potentially reducing immune complex production and deposition in kidney tissues, which can lead to ESKD necessitating transplantation.

Sibeprenlimab, initially known as VIS649, was designed by Visterra, Inc., a subsidiary of Otsuka. It selectively binds to and inhibits APRIL, playing a significant role in the disease's 4-hit pathogenic process. By countering APRIL, sibeprenlimab reduces levels of Gd-IgA1, thus limiting immune complex formation and auto-antibody production, which are critical factors in IgAN progression. Lowering immune complex generation should lead to decreased kidney deposition, reduced proteinuria, and less inflammation, potentially slowing kidney damage progression towards ESKD.

IgAN commonly manifests in adults aged 20-40 and is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. Despite supportive care, there is a pressing need for treatments addressing the condition’s root cause. Continued research remains essential for discovering new opportunities in understanding and treating IgAN.

APRIL, a cytokine within the tumor necrosis factor family, is crucial to IgAN's pathogenesis and progression. It aids B cells in survival and class switching to produce pathogenic IgA, which forms harmful immune complexes in the kidneys.