Sibeprenlimab Reduces Protein Levels in Adults with IgA Nephropathy shows Phase 3 VISIONARY study

The Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. announced promising interim results from their ongoing Phase 3 trial of sibeprenlimab, an investigational treatment for immunoglobulin A nephropathy (IgA nephropathy) in adults. This announcement comes as a significant milestone in the search for effective therapies for this progressive kidney disease, which can lead to end-stage kidney disease (ESKD).

Sibeprenlimab is a monoclonal antibody that targets APRIL (A PRoliferation-Inducing Ligand), playing a crucial role in regulating the immune response that contributes to IgA nephropathy. By inhibiting the production of Gd-IgA1 and the formation of harmful immune complexes, sibeprenlimab aims to mitigate the disease's progression. The treatment has already gained Breakthrough Therapy designation following encouraging results from the Phase 2 ENVISION clinical trial.

The interim analysis, conducted by an independent data monitoring committee, revealed that the Phase 3 VISIONARY study met its primary endpoint. Results showed that sibeprenlimab led to a statistically significant reduction in the 24-hour urine protein-to-creatine ratio compared to placebo after nine months of treatment. This multicenter, randomized, double-blind, placebo-controlled trial involved approximately 530 adult patients receiving standard care, making it the largest study in this patient population.

Dr. John Kraus, executive vice president and chief medical officer of Otsuka Pharmaceutical Development & Commercialization, remarked on the findings in a press release: “The positive interim data from this trial suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease.” He expressed gratitude to the participants, caregivers, and investigators involved in the study.

Brian Pereira, CEO of Visterra, Inc., an Otsuka U.S. affiliate, also commented on the significance of the results, noting sibeprenlimab's potential to offer a much-needed, disease-modifying treatment option for IgA nephropathy patients.

The ongoing Phase 3 study continues to assess kidney function changes over 24 months, using an estimated glomerular filtration rate (eGFR). The study is expected to conclude in early 2026, with further analyses planned to fully understand sibeprenlimab's therapeutic potential. Otsuka aims to review these interim results with the FDA to facilitate a possible regulatory submission for accelerated approval.

About Sibeprenlimab

Sibeprenlimab (formerly VIS649) is an investigational monoclonal antibody developed by Visterra, Inc., a subsidiary of Otsuka. It targets APRIL (A PRoliferation-Inducing Ligand), a key player in the pathogenic cascade of IgA nephropathy. By blocking APRIL, sibeprenlimab aims to reduce levels of immunoglobulin A (IgA) and Gd-IgA1, potentially lowering auto-antibody production and immune complexes. This reduction may lead to fewer immune complex deposits in the kidneys, decreasing proteinuria and inflammation.

The drug's mechanism could slow kidney damage and progression toward ESKD by addressing a specific driver of nephron loss in IgA nephropathy. Early-stage trials have shown promise, highlighting sibeprenlimab's potential to provide a new therapeutic option for patients with this challenging condition.