Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for sibeprenlimab, an investigational monoclonal antibody developed to treat adults with immunoglobulin A nephropathy (IgAN). The application has been granted priority review, with a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2025.
Sibeprenlimab is designed to selectively inhibit APRIL (A Proliferation-Inducing Ligand), a key protein involved in the pathogenesis of IgAN. IgAN is characterized by the four-hit process, beginning with the production of galactose-deficient IgA1 (Gd-IgA1), followed by the formation of autoantibodies targeting Gd-IgA1. These immune complexes deposit in the kidney’s glomerular mesangium, leading to inflammation and progressive kidney damage.
The treatment is formulated as a single-dose prefilled syringe for subcutaneous injection every four weeks, allowing for self-administration and greater convenience for patients.
The BLA submission is supported by robust clinical data from the Phase 3 VISIONARY trial (NCT05248646) and the Phase 2 ENVISION trial (NCT04287985). In the Phase 3 study, sibeprenlimab met its primary endpoint at a prespecified interim analysis, showing a statistically significant and clinically meaningful reduction in 24-hour urinary protein-to-creatinine ratio (uPCR) after nine months compared to placebo.
Sibeprenlimab has also received Breakthrough Therapy designation for the treatment of IgAN based on encouraging results from the Phase 2 ENVISION study
IgA nephropathy remains a serious and progressive autoimmune kidney disease with limited treatment options,” said Dr. John Kraus, Executive Vice President and Chief Medical Officer at OPDC. “Our focus has been on addressing complex conditions in nephrology, and sibeprenlimab has the potential to provide significant clinical benefits with the added convenience of monthly at-home administration.
IgAN can progress to end-stage kidney disease (ESKD) in many patients, even under current standard care. By targeting APRIL, sibeprenlimab offers a novel approach to interrupt the disease’s root mechanisms, potentially slowing or preventing kidney damage and reducing the need for dialysis or transplantation
About sibeprenlimab
Sibeprenlimab (formerly VIS649) was designed and engineered by Visterra, Inc., a wholly owned subsidiary of Otsuka. Pre-clinical and early-stage trials of sibeprenlimab were also conducted by Visterra.
Sibeprenlimab is an investigational monoclonal antibody that selectively binds to and inhibits the activity of APRIL and plays a key role in the 4-hit process. By binding and inhibiting APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (IgA) and Gd-IgA1 levels. Lower levels of Gd-IgA1 provide less substrate for immune complex formation, and may also result in reduced auto-antibody production. Decreased immune complex creation should result in diminished deposition in the kidney, and reduced proteinuria and kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD.2,4,5,6 By inhibiting APRIL, sibeprenlimab may help address one of the IgAN-specific drivers for nephron loss.
