IgA Nephropathy Drug Voyxact Meets Two-Year Kidney Function Endpoint, Advancing Full Approval Application

The treatment goal for IgA nephropathy is shifting from reducing urinary protein to further slowing the loss of kidney function. Otsuka Pharmaceutical announced two-year results from the Phase 3 VISIONARY trial, stating that the APRIL inhibitor Voyxact (sibeprenlimab-szsi) stabilized estimated glomerular filtration rate (eGFR) and showed evidence of improvement compared with placebo, meeting the trial’s key secondary endpoint.

VISIONARY is a global, randomized, double-blind, placebo-controlled study. This analysis measured the rate of change in kidney function using the annualized eGFR slope over 24 months and compared participants’ mean change in eGFR from baseline at Month 24. Otsuka said both analyses achieved statistical significance. However, only topline results have been released so far, without details on the actual differences, confidence intervals, number of kidney failure events, or outcomes across subgroups.

IgA nephropathy arises from an abnormal immune response in which pathogenic IgA and its immune complexes accumulate in the kidneys, causing long-term inflammation and tissue damage. Voyxact is a humanized monoclonal antibody administered by subcutaneous injection once every four weeks. By blocking the proliferation-inducing ligand APRIL, it reduces the production of galactose-deficient IgA1, with the aim of reducing the persistent immune stimulation that damages the kidneys upstream in the disease process, without broadly depleting B cells.

Background

In November 2025, the U.S. Food and Drug Administration approved Voyxact through the accelerated approval pathway for adults with primary IgA nephropathy who are at risk of disease progression. The decision was based on the first 320 participants in VISIONARY who completed the nine-month assessment: proteinuria decreased by 50% in the treatment group, while it increased by 2% in the placebo group. However, proteinuria is a surrogate endpoint, and the regulator explicitly stated at the time that whether the drug could slow the long-term decline in kidney function had not yet been established.

The two-year results therefore do more than add another efficacy figure; they directly address the confirmatory requirement left by the accelerated approval. Otsuka is making a rolling submission of a supplemental biologics license application, seeking to convert the U.S. approval to traditional approval, and plans to use the complete data to support marketing applications in other markets. If subsequent reviews confirm the clinical benefit, selective APRIL inhibition will gain more comprehensive evidence of long-term kidney protection and could also raise the development bar for new drugs targeting the same indication.

Regarding safety, Otsuka said the two-year data were consistent with the previous interim analysis and that the overall profile was comparable to placebo. Existing FDA data identify infections and injection-site reactions as the main areas of concern. Because the full frequencies of adverse events, treatment discontinuations, and serious infections have not yet been disclosed, it is currently impossible to independently determine whether the long-term risks are truly comparable.

What will ultimately determine the significance of these results is whether the complete data can demonstrate that the magnitude of benefit is clinically meaningful and whether patients with different baseline risk levels benefit equally. Until the results are presented at an academic conference or published in a peer-reviewed paper, the more cautious conclusion is that Voyxact has met the prespecified two-year statistical endpoint for kidney function, but the actual extent of its kidney-protective effect and the patient population to which it applies still await complete analysis.