FDA Grants Priority Review to Sibeprenlimab for the Kidney Disease IgAN

The FDA has accepted for priority review the biologics license application (BLA) for sibeprenlimab to treat patients with immunoglobulin A nephropathy (IgAN), a chronic kidney disease. Regulators have granted the BLA priority review and given sibeprenlimab a Prescription Drug User Fee Act (PDUFA) target action date of Nov. 28, 2025.

If approved, sibeprenlimab would be offered as a prefilled syringe for subcutaneous injection every four weeks, intended for at-home self-administration.

IgAN is a progressive autoimmune condition that can lead to end-stage kidney disease. A recent study has estimated the incidence and prevalence of IgAN in 2021 to be between 198,887 and 208,184 people. But patients with IgAN may be undiagnosed because the disease is asymptomatic and not routinely screened for. “Long-term outcomes are often poor, particularly because many patients are diagnosed late in the course of their disease,” Jonathan Barrat, Ph.D., the Mayer Professor of Renal Medicine and Honorary Consultant Nephrologist at the University of Leicester, said in an interview last year with Managed Healthcare Executive.

Related: Looking to the Future of IgA Nephropathy Treatment

Developed by Visterra, an affiliate of Otsuka Pharmaceutical, sibeprenlimab is a monoclonal antibody that inhibits the activity of APRIL (A PRoliferation-Inducing Ligand), a cytokine in the tumor necrosis factor family. By binding and inhibiting APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (IgA) and Gd-IgA1 levels, which helps to decrease immune complex creation.

John Kraus, M.D., Ph.D.

“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,” John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, said in a news release when the application was submitted in March 2025.

The BLA is supported by the phase 3 VISIONARY clinical trial, which met its primary endpoint at the prespecified interim analysis, and results from the phase 2 ENVISION clinical trial. In the phase 3 trial, sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatine ratio (uPCR) after nine months of treatment compared with placebo.

The VISIONARY study is a placebo-controlled trial that recruited about 530 adult patients with IgA nephropathy who were receiving standard-of-care therapy (an ACE inhibitor or ARB +/- SGLT2 inhibitor). The trial was designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks compared with placebo.

An interim analysis of the phase 3 trial was released in October 2024, which showed that sibeprenlimab produced a statistically significant and clinically meaningful reduction in the 24-hour urine protein-to-creatine ratio after nine months of treatment.

The positive results from the phase 2 ENVISION trial led to a breakthrough designation from the FDA. These results were published in The New England Journal of Medicine in November 2023. The primary endpoint was the change from baseline in the log-transformed 24-hour urinary protein-to-creatinine ratio at month 12. Secondary endpoints included the change from baseline in the estimated glomerular filtration rate (eGFR) at month 12.

The ENVISION trial found that in patients with IgA nephropathy, 12 months of treatment with sibeprenlimab resulted in a significantly greater decrease in proteinuria than placebo.