Otsuka Files BLA for Sibeprenlimab for IgA Nephropathy

Otsuka Pharmaceutical has announced the filing of a Biologics License Application (BLA) with the US Food and Drug Administration (FDA) for sibeprenlimab in adults with immunoglobulin A nephropathy (IgAN).1

According to a March 31, 2025, press release from the company, the BLA submission is supported by results from the phase 2 ENVISION and the phase 3 VISIONARY clinical trials. VISIONARY met its primary endpoint at the prespecified interim analysis, demonstrating treatment with sibeprenlimab led to a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatine ratio compared with placebo after 9 months of treatment.1

“This BLA for sibeprenlimab represents a significant achievement in our journey to bring innovative treatments to patients with IgA nephropathy," Brian Pereira, MD, CEO of Visterra, said in a statement.1 “We look forward to the FDA’s review and are grateful for the opportunity to help develop a treatment that could alter the course of this challenging kidney disease and improve patient outcomes.”

An investigational monoclonal antibody that selectively inhibits the activity of A PRoliferation-Inducing Ligand (APRIL), sibeprenlimab, formerly known as VIS649, was designed and engineered by Visterra, a wholly owned subsidiary of Otsuka, which also conducted pre-clinical and early-stage trials of sibeprenlimab.1

As described in the release from Otsuka, sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every 4 weeks intended for self-administration or administration by a caregiver.1

By binding and inhibiting APRIL, sibeprenlimab may help reduce IgA and Gd-IgA1 levels. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward end-stage kidney disease. By inhibiting APRIL, it may also help address one of the IgAN-specific drivers for nephron loss.1

In 2024, the FDA granted a Breakthrough Therapy designation for sibeprenlimab following favorable results of the phase 2 ENVISION clinical trial.2 It is now being evaluated in the multicenter, randomized, double-blind, placebo-controlled VISIONARY trial, which enrolled approximately 530 adult patients with IgAN who were receiving standard-of-care therapy, defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor.1

The primary efficacy endpoint is the change in 24-hour uPCR at 9 months compared with baseline. The secondary endpoint is the annualized slope of eGFR estimated over ~24 months. At the prespecified interim analysis, sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour uPCR after 9 months of treatment.1

“This BLA filing marks an important milestone in Otsuka's commitment to address unmet needs in kidney diseases,” John Kraus, MD, PhD, executive vice president and chief medical officer of Otsuka Pharmaceutical, said in a statement.1 “Sibeprenlimab’s unique mechanism of action inhibits the activity of APRIL and addresses an IgA-specific driver of kidney loss in IgA nephropathy. APRIL is a cytokine that plays a key role in the pathogenesis of IgA nephropathy and we are optimistic about its potential to be an important treatment option for this progressive kidney disease.”

References

1. Otsuka. Otsuka Files Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy. March 31, 2025. Accessed March 31, 2025. https://www.otsuka-us.com/news/otsuka-files-biologics-license-application-bla-sibeprenlimab-treatment-immunoglobulin

2. Otsuka. Sibeprenlimab Receives U.S. FDA Breakthrough Therapy Designation for the Treatment of Immunoglobulin A Nephropathy. February 16, 2024. Accessed March 31, 2025. https://www.otsuka-us.com/news/sibeprenlimab-receives-us-fda-breakthrough-therapy-designation-treatment-immunoglobulin