Two-Year Kidney Function Curve Nearly Flat: Voyxact Phase 3 Trial Adds Long-Term Evidence in IgA Nephropathy

The true test of IgA nephropathy treatment is not merely whether it reduces proteinuria in the short term, but whether it can preserve kidney function that would otherwise decline year by year. Otsuka Pharmaceutical announced two-year results from the Phase 3 VISIONARY trial: among patients receiving Voyxact (sibeprenlimab-szsi), the annualized change in estimated glomerular filtration rate (eGFR) was +0.3 mL/min/1.73 m² per year, compared with −4.2 in the placebo group, yielding a statistically significant between-group treatment difference of +4.5.

This global, randomized, double-blind, placebo-controlled trial evaluated the 24-month eGFR slope as a key secondary endpoint. The 95% confidence interval for the treatment group was −0.4 to 0.9, meaning the data support “stable kidney function” more strongly; the point estimate alone cannot establish that kidney function actually improved. By comparison, the placebo group’s 95% confidence interval was −4.9 to −3.6, showing a continued decline. The least-squares mean change from baseline to month 24 was also +1.3 in the treatment group and −7.9 mL/min/1.73 m² in the placebo group, for a between-group difference of +9.2.

Sibeprenlimab is a humanized monoclonal antibody administered by subcutaneous injection once every four weeks that selectively blocks APRIL. This immune signal can promote the production of galactose-deficient IgA1, which forms immune complexes and deposits in the kidneys and is considered an important part of the disease process in IgA nephropathy. The drug therefore seeks to reduce pathogenic IgA upstream rather than broadly depleting B cells.

VISIONARY had previously met its primary endpoint: after nine months of treatment, the 24-hour urine protein-to-creatinine ratio was reduced by approximately 51% compared with placebo. Based on this result, the US Food and Drug Administration granted accelerated approval to Voyxact in November 2025 for adults with primary IgA nephropathy at risk of disease progression. The two-year eGFR data now add evidence more closely related to long-term organ protection. Otsuka is incorporating the data into its rolling submission of a supplemental biologics application seeking traditional approval and plans to support marketing applications in other regions.

Regarding safety, Otsuka said overall adverse-event rates were similar between the two groups, at 90.7% in the treatment group and 90.0% in the placebo group. Infection-related events occurred in 51.4% and 51.0%, respectively, while injection-site reactions occurred in 35.1% and 32.2%. No new safety signals were identified over the two years. These data continue the trend seen in the earlier interim analysis, but currently come mainly from company disclosures and conference reports. Full group-level data, treatment discontinuations, and detailed adverse-event analyses still require assessment through formal publication.

The results suggest that Voyxact may reduce the rate of kidney function decline in patients with IgA nephropathy to a level close to that associated with normal physiological aging, giving the findings greater clinical significance than observing changes in proteinuria alone. However, the eGFR slope remains a surrogate endpoint. The trial has not yet directly shown that the drug can reduce dialysis, kidney transplantation, or death, and two years of follow-up cannot determine whether the effect can be sustained over the long term. The open-label extension study and a subsequent full paper will determine whether this striking curve translates into durable kidney outcomes.