Otsuka Reports Final Phase 3 VOYXACT Results in IgA Nephropathy

PRINCETON, N.J., and TOKYO, Japan — October 22, 2026

VISIONARY Demonstrates Favorable Kidney Outcomes

The global, randomized, double-blind, placebo-controlled Phase 3 VISIONARY study evaluated VOYXACT in adults with primary IgAN at risk of disease progression. The primary endpoint assessed the change in 24-hour urine protein-to-creatinine ratio (uPCR-24h) after nine months, while secondary endpoints included annualized estimated glomerular filtration rate (eGFR) slope over two years and change in eGFR at Month 24. The final analysis showed that fewer patients receiving VOYXACT experienced key measures of sustained kidney function decline. A sustained eGFR reduction of at least 40% occurred in 1 patient receiving VOYXACT versus 28 receiving placebo; sustained doubling of serum creatinine occurred in 0 versus 13 patients, respectively. Sustained eGFR below 15 mL/min/1.73 m² occurred in 1 patient in the VOYXACT group compared with 10 in the placebo group. No patient receiving VOYXACT initiated kidney replacement therapy, compared with 5 patients receiving placebo. Kidney function measurements also favored treatment. The annualized eGFR slope was +0.3 mL/min/1.73 m² per year with VOYXACT versus −4.2 mL/min/1.73 m² per year with placebo, a treatment difference of +4.5 mL/min/1.73 m² per year (95% CI, 3.6–5.4; p<0.0001). At Month 24, the least-squares mean change from baseline in eGFR was +1.3 mL/min/1.73 m² with VOYXACT compared with −7.9 mL/min/1.73 m² with placebo, a group difference of +9.2 mL/min/1.73 m² (95% CI, 7.1–11.4; p<0.0001). The company reported that the treatment effect was consistent across prespecified subgroups, including baseline proteinuria, eGFR and use of sodium-glucose cotransporter-2 inhibitors (SGLT2i).

Proteinuria Reduction and Safety Profile Maintained

VOYXACT also produced sustained reductions in proteinuria, with a 61.3% reduction in 24-hour uPCR at Month 24. Among participants with hematuria at baseline, 78.6% of those receiving VOYXACT had a negative dipstick result, compared with 20.2% receiving placebo. The overall safety profile remained comparable between the treatment and placebo groups over two years. Overall adverse events occurred in 90.7% of patients receiving VOYXACT and 90.0% receiving placebo. Infections and infestations were reported in 51.4% and 51.0%, respectively, while injection-site reactions occurred in 35.1% and 32.3%. Otsuka reported no new safety signals, with serious infections occurring in 1.9% of the VOYXACT group compared with 4.0% of the placebo group. Serious and severe adverse events and treatment discontinuations were also reported at lower rates with VOYXACT. Dana Rizk, M.D., a VISIONARY site principal investigator and steering committee co-chair, said the results showed sustained kidney function stabilization and a substantial reduction in kidney failure events. Otsuka Chief Medical Officer John Kraus, M.D., Ph.D., said the findings reinforce the potential role of selective APRIL inhibition in preserving kidney function. The results support further evaluation of VOYXACT’s long-term clinical benefit, although the current accelerated approval remains based on proteinuria reduction.

Selective APRIL Inhibition Advances IgAN Treatment Research

VOYXACT is a humanized monoclonal antibody that binds to and blocks APRIL, a protein involved in the production of galactose-deficient immunoglobulin A1 (Gd-IgA1), which contributes to IgAN pathogenesis. By inhibiting APRIL, the treatment reduces levels of Gd-IgA1 implicated in the disease. VOYXACT is administered as a self-injected subcutaneous dose once every four weeks. IgAN is a progressive, immune-mediated kidney disease characterized by the accumulation of Gd-IgA1-containing immune complexes in the kidneys and can lead to progressive loss of kidney function and kidney failure. Otsuka reported that VISIONARY achieved the 2025 Kidney Disease: Improving Global Outcomes (KDIGO) treatment goal of slowing kidney function decline to near-physiologic rates for most adults. The company has completed its rolling sBLA submission to the FDA for traditional approval, including the two-year eGFR findings. Additional research is also underway, including a Phase 3 open-label study evaluating sibeprenlimab in pediatric participants aged 2–17 years with IgAN and a Phase 2 study in primary membranous nephropathy, immune-mediated focal segmental glomerulosclerosis and minimal change disease. VOYXACT remains subject to important safety considerations, including possible increased infection risk due to immunosuppression, and live vaccines are not recommended during treatment. The long-term effect of VOYXACT on kidney function decline has not yet been established as part of its current accelerated approval and requires confirmation of clinical benefit.

Source: Otsuka Pharmaceutical,release