Otsuka Pharmaceutical has announced promising interim Phase III results for sibeprenlimab in the treatment of the rare and progressive autoimmune kidney disease immunoglobulin A nephropathy (IgAN).
The data, presented from the VISIONARY trial, demonstrated a statistically significant and clinically meaningful reduction in proteinuria — a key indicator of disease progression.
Specifically, patients receiving sibeprenlimab experienced a 51.2% reduction in 24-hour urine protein-to-creatinine ratio (uPCR) after nine months of treatment compared to placebo, exceeding expectations.
Proteinuria reduction is an established surrogate marker for long-term kidney outcomes in IgAN.
IgAN is a chronic, immune-mediated kidney disease that typically presents in adults between the ages of 20 and 40. Over time, it often progresses to end-stage kidney disease (ESKD), placing a substantial long-term burden on patients.
The condition is marked by the buildup of pathogenic galactose-deficient IgA1 (Gd-IgA1) immune complexes in the kidneys, which triggers inflammation and leads to a gradual loss of kidney function.
While supportive therapies are available, there remains a significant unmet need for treatments that directly target the underlying mechanisms of the disease.
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Sibeprenlimab is a monoclonal antibody that targets APRIL (A Proliferation-Inducing Ligand), which promotes the production of Gd-IgA1. By neutralizing APRIL, sibeprenlimab is designed to reduce the production of Gd-IgA1.
“We are confident about the potential of sibeprenlimab and are grateful to the patients who are helping to further the science by participating in these important trials,” said Otsuka’s executive vice president and chief medical officer, John Kraus, MD, PhD, in the company’s news release.
“Proteinuria control is an important independent predictor for long-term prognosis, and this interim data reinforces our belief that selectively targeting APRIL has the potential to be an effective and safe approach for this progressive and irreversible kidney disease.”
The Phase III VISIONARY trial, the largest IgAN trial to date, enrolled over 500 adults who were already on standard-of-care therapies, such as ACE inhibitors or ARBs, with or without SGLT2 inhibitors. Patients were randomized to receive either sibeprenlimab at a dose of 400 mg administered subcutaneously every four weeks or a placebo.
The interim analysis also revealed a favorable safety profile for sibeprenlimab. Treatment-emergent adverse events (TEAEs) occurred in 76.3% of patients receiving the drug compared to 84.5% in the placebo group, and serious TEAEs were reported in 3.9% versus 5.4%, respectively.
Related: Sibeprenlimab Reduces Proteinuria in Phase III IgA Nephropathy Trial
Last year, Otsuka reported that sibeprenlimab reached its primary endpoint, showing a statistically significant reduction in proteinuria at nine months compared to placebo.
If approved, sibeprenlimab would become the first anti-APRIL monoclonal antibody authorized for the treatment of IgAN. And its monthly, self-administered dosing could offer a convenient and disease-modifying approach that targets the underlying biology of IgAN.
In March 2025, Otsuka submitted a Biologics License Application (BLA) for sibeprenlimab. The FDA granted the application Priority Review in late May and set a target action date of November 28, 2025.
If approved, sibeprenlimab would join a growing IgAN treatment market that now includes Calliditas Therapeutics’ Tarpeyo (budesonide) that was approved last year, Novartis’ recently introduced Fabhalta (iptacopan) and Vanrafia (atrasentan) as well as Travere Therapeutics’ Filspari (sparsentan).
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