APRIL Inhibitor Sibeprenlimab Preserves Kidney Function in IgA Nephropathy

Sibeprenlimab, a humanized monoclonal antibody that selectively inhibits the cytokine A proliferation-inducing ligand (APRIL), stabilized the estimated glomerular filtration rate (eGFR) slope over 24 months in adults with IgA nephropathy. The findings come from the final analysis of the phase 3 VISIONARY trial, published in NEJM.

The investigators describe APRIL as a key driver of IgA nephropathy. Preliminary results for the trial’s primary end point, the change in 24-hour urinary protein-to-creatinine ratio at 9 months, were reported previously. This analysis reports secondary end points, including eGFR outcomes. The trial was funded by Otsuka Pharmaceutical Development and Commercialization.

In the double-blind trial, 510 adults were randomly assigned to subcutaneous sibeprenlimab 400mg (259 patients) or placebo (251 patients) every 4 weeks. The key secondary end point was the annualized eGFR slope over 24 months. It was 0.3mL/min/1.73m² per year with sibeprenlimab and −4.2mL/min/1.73m² per year with placebo (between-group difference, 4.5mL/min/1.73m² per year; 95% CI, 3.6-5.4). The least-squares mean difference in eGFR change from baseline to 24 months was 9.2mL/min/1.73m².

A composite kidney end point of kidney-function decline or kidney failure occurred in 1 patient (0.4%) in the sibeprenlimab group and 28 patients (11.2%) in the placebo group. Rates of adverse events were similar between the sibeprenlimab and placebo groups (90.7% and 90.0%). Serious adverse events occurred in 8.1% and 12.7%, respectively, and serious infections in 1.9% and 4.0%. No deaths were reported.

The investigators concluded that sibeprenlimab stabilized the eGFR slope over 24 months, a finding they described as consistent with a reduced risk of kidney-function decline.

Source: Rizk DV, Barratt J, Suzuki Y, et al. Sibeprenlimab in IgA nephropathy — final phase 3 trial analysis. N Engl J Med. Published online October 22, 2026. doi:10.1056/NEJMoa2609127