New VISIONARY Analyses Reinforce Benefits of APRIL Inhibition With Sibeprenlimab in IgAN

New analyses from the phase 3 VISIONARY trial evaluating Otsuka Pharmaceutical Development & Commercialization’s sibeprenlimab-szsi (Voyxact) in adults with IgA nephropathy (IgAN) at risk for disease progression highlight clinically meaningful improvements across key markers of IgAN.

The data were presented at the 2026 ISN World Congress of Nephrology and reinforce the potential of selectively inhibiting A PRoliferation Inducing Ligand (APRIL), a central driver of disease biology, to meaningfully impact patient outcomes.

“The new VISIONARY analyses highlight the differentiated clinical profile of sibeprenlimab and the potential clinical impact of targeting a key immune driver of the disease,” John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka, said in a statement. “In addition to meaningful reductions in proteinuria, the observed improvements in hematuria provide complementary evidence of an effect on underlying disease activity. Together, these findings reinforce the potential of [sibeprenlimab] to meaningfully improve clinical outcomes for adult IgAN patients at risk for disease progression.”

Sibeprenlimab is a humanized monoclonal antibody that binds to and blocks APRIL, which plays a key role in the 4-hit process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression by promoting the production of pathogenic galactose-deficient IgA1 (Gd-IgA1). Inhibition of APRIL results in reduced levels of serum Gd-IgA1, which is implicated in the pathogenesis of IgAN. Sibeprenlimab is a self-administered, subcutaneous injection dosed every 4 weeks.

It was granted accelerated approval by the US Food and Drug Administration for reducing proteinuria in primary IgAN in November 2025 based on 12-month data from the VISIONARY trial showing a 54.3% placebo-adjusted reduction in geometric mean 24-hour urine protein-to-creatinine ratio (UPCR) from baseline.

Of note, the accelerated approval was based on reduction of proteinuria. It has not been established whether sibeprenlimab slows kidney function decline over the long-term in patients with IgAN, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

The interim VISIONARY analyses presented at WCN showed a greater and faster proportion of patients achieving negative microscopic hematuria (0–5/HPF), an exploratory endpoint reflecting improvement in glomerular injury in IgAN. Among global patients with hematuria at baseline, 82.5% of patients receiving sibeprenlimab were negative for microscopic hematuria at week 48 compared with 52.6% of patients receiving placebo. Median time to achieve negativity for microscopic hematuria (0–5/HPF) was 9 weeks with sibeprenlimab versus 24 weeks with placebo.

As described in a press release from Otsuka, the findings complement robust proteinuria reductions observed with sibeprenlimab. Of note, the safety profile was comparable between sibeprenlimab and placebo.

In a previously prespecified interim analysis of the global main cohort of VISIONARY presented at the European Renal Association (ERA) congress in 2025, sibeprenlimab met the primary endpoint, demonstrating a -51.2% (P <.0001) placebo-adjusted reduction in 24-hour UPCR at 9 months.

The VISIONARY trial is ongoing to evaluate the safety and efficacy of sibeprenlimab in preserving kidney function based on estimated glomerular filtration rate slope over a 24-month treatment period.

References

1. Otsuka. Otsuka Showcases New Efficacy and Safety Data of VOYXACT® (sibeprenlimab-szsi) in Patients with IgA Nephropathy (IgAN) at the 2026 ISN World Congress of Nephrology Highlighting the Impact of APRIL Inhibition. March 25, 2026. Accessed April 2, 2026. https://www.businesswire.com/news/home/20260324322305/en/Otsuka-Showcases-New-Efficacy-and-Safety-Data-of-VOYXACT-sibeprenlimab-szsi-in-Patients-with-IgA-Nephropathy-IgAN-at-the-2026-ISN-World-Congress-of-Nephrology-Highlighting-the-Impact-of-APRIL-Inhibition

2. Campbell P. FDA Awards Accelerated Approval to Sibeprenlimab in IgA Nephropathy. HCPLive. November 25, 2025. Accessed April 2, 2026. https://www.hcplive.com/view/fda-awards-accelerated-approval-to-sibreprenlimab-in-iga-nephropathy

3. Campbell P. ERA 2025: Sibeprenlimab Halves Proteinuria in IgAN in Phase 3 VISIONARY Trial. HCPLive. June 6, 2025. Accessed April 2, 2026. https://www.hcplive.com/view/era-2025-sibeprenlimab-halves-proteinuria-in-igan-in-phase-3-visionary-trial