VOYXACT Becomes First APRIL Inhibitor to Stabilize eGFR in Phase 3 VISIONARY Trial for IgA Nephropathy

Otsuka Pharmaceutical reported positive topline results from the Phase 3 VISIONARY trial (NCT05248646), showing that VOYXACT® (sibeprenlimab-szsi) significantly stabilized kidney function over two years in adults with primary IgA nephropathy (IgAN).

The selective APRIL inhibitor demonstrated statistically significant improvements in estimated glomerular filtration rate (eGFR) decline compared with placebo, while maintaining a favorable safety profile consistent with earlier analyses.

The results confirm and extend the favorable 12-month interim kidney function findings reported at the 2026 ERA Congress, providing the complete 24-month Phase 3 dataset.

The findings complete the Phase 3 dataset supporting the company’s rolling supplemental Biologics License Application (sBLA) for traditional U.S. FDA approval. VOYXACT received accelerated approval in November 2025 based on its ability to reduce proteinuria in adults with IgAN at risk of disease progression.

Selective APRIL Inhibition Supports Long-Term Kidney Protection

IgA nephropathy is a chronic immune-mediated kidney disease characterized by the deposition of galactose-deficient IgA1 (Gd-IgA1) immune complexes in the kidneys, leading to progressive loss of renal function and, in many patients, kidney failure.

VOYXACT is a humanized monoclonal antibody that selectively blocks APRIL (A Proliferation-Inducing Ligand), a key driver of pathogenic Gd-IgA1 production. By targeting APRIL without broadly depleting B cells, the therapy reduces disease-causing IgA production while preserving broader immune function. The latest results reinforce selective APRIL inhibition as a disease-modifying strategy capable of slowing the underlying progression of IgAN rather than simply controlling clinical manifestations.

 Kidney Function and Safety Outcomes

The randomized, double-blind, placebo-controlled Phase 3 trial evaluated adults with primary IgAN at risk of disease progression.

The primary endpoint measured the change in 24-hour urine protein-to-creatinine ratio (uPCR) after nine months of treatment. VOYXACT previously met this endpoint, leading to accelerated FDA approval.

The newly reported two-year analyses showed statistically significant stabilization of kidney function based on both annualized eGFR slope and mean change from baseline in eGFR compared with placebo. The results also demonstrated evidence of kidney function improvement over two years and aligned with the 2025 KDIGO treatment goal of limiting kidney function decline to near physiological rates. Otsuka also reported robust reductions in the risk of progression to kidney failure.

VOYXACT remained well tolerated throughout the study, with adverse events comparable to placebo and no new safety signals identified.

Regulatory Path

John Kraus, MD, PhD, Executive Vice President and Chief Medical Officer at Otsuka, said the two-year findings represent an important advance for patients with IgAN by demonstrating clinically meaningful preservation of kidney function beyond proteinuria reduction. He added that the results strengthen evidence for selective APRIL inhibition as a disease-modifying approach and support continued discussions with the U.S. FDA on traditional approval.

Otsuka plans to submit the complete VISIONARY analyses to global regulatory authorities and present the data at an upcoming scientific congress. The company is also continuing long-term evaluation of VOYXACT in the ongoing open-label extension study (NCT05248659), which will provide additional evidence on the durability of treatment benefit and long-term safety.

Reference

Otsuka Reports Positive Phase 3 VISIONARY Two-Year eGFR Results Demonstrating VOYXACT® (sibeprenlimab-szsi) Prevented Progression to Kidney Failure and Improved Kidney Function in IgA Nephropathy (IgAN) | Otsuka US