Phase 3 VISIONARY results show VOYXACT stabilized kidney function in IgA nephropathy, meeting its key secondary endpoint with placebo-like safety.
Written by: Mayuresh Salvi, PharmD
Reviewed by: Pharmacally Editorial Team
Otsuka Pharmaceuticals have announced positive two-year results from the Phase 3 VISIONARY trial showing that VOYXACT® (sibeprenlimab-szsi) significantly stabilized kidney function in adults with primary IgA nephropathy (IgAN) at risk of disease progression. Presented during a late-breaking oral presentation at GlomCon Hawaii 2026, the study met its key secondary endpoint and demonstrated that VOYXACT reduced kidney function decline to the physiologic rate defined by kidney disease: Improving Global Outcoms (KDIGO) guidelines while maintaining a safety profile comparable to placebo.
Phase 3 VISIONARY Trial
VISIONARY (NCT05248646) is a global, randomized, double-blind, placebo-controlled Phase 3 study evaluating VOYXACT in adults with primary IgAN at risk of disease progression. The trial previously met its primary endpoint by significantly reducing proteinuria after nine months of treatment, leading to the drug’s accelerated U.S. Food and Drug Administration approval in November 2025. The newly reported 24-month analysis evaluated kidney function using annualized estimated glomerular filtration rate (eGFR) slope.
VOYXACT Significantly Preserved Kidney Function
The study achieved its key secondary endpoint, with patients receiving VOYXACT showing an annualized estimated eGFR slope of +0.3 mL/min/1.73 m²/year (95% CI, -0.4 to 0.9) compared with -4.2 mL/min/1.73 m²/year (95% CI, -4.9 to -3.6) for placebo. This represented a statistically significant treatment effect of +4.5 mL/min/1.73 m²/year (95% CI, 3.6 to 5.4; p<0.0001).
At 24 months, the least-square mean change from baseline in eGFR was +1.3 mL/min/1.73 m² (95% CI, -0.3 to 2.8) with VOYXACT versus -7.9 mL/min/1.73 m² (95% CI, -9.5 to -6.4) with placebo, corresponding to a treatment difference of +9.2 mL/min/1.73 m² (95% CI, 7.1 to 11.4; p<0.0001).
According to Otsuka, VOYXACT is the first IgAN treatment to achieve the KDIGO therapeutic goal of reducing kidney function decline to the physiologic rate, defined as less than 1 mL/min/1.73 m²/year for most adults. The findings also build on previously reported reductions in galactose-deficient IgA1 (Gd-IgA1), proteinuria, and hematuria, supporting selective APRIL inhibition as a disease-modifying therapeutic approach.
Safety Profile Remained Comparable to Placebo
VOYXACT maintained a favorable safety profile throughout the two-year study. Overall adverse events occurred in 90.7% of patients receiving VOYXACT compared with 90.0% of those receiving placebo. Rates of infections and infestations (51.4% vs 51.0%) and injection-site reactions (35.1% vs 32.2%) were similar between treatment groups.
No new safety signals were identified. Serious infections were less frequent with VOYXACT than placebo (1.9% vs 4.0%), while serious adverse events, severe adverse events, and treatment discontinuations were also reported less often in the VOYXACT group.
Expert Perspective
“For nephrologists, stabilization of kidney function in IgAN patients represents a major advancement in the clinical management of this disease,” said Dr. Dana Rizk, Professor of Medicine in the Division of Nephrology at the University of Alabama at Birmingham and co-chair of the VISIONARY steering committee.
She added that the two-year results achieved the KDIGO treatment goal of reducing kidney function decline to near physiologic levels and, together with the consistent safety profile, offer new hope for improving long-term outcomes in patients with this progressive kidney disease.
Otsuka also noted that VISIONARY is the largest Phase 3 trial conducted in IgA nephropathy and that the findings further support selective APRIL inhibition as a durable disease-modifying strategy.
Regulatory Status
VOYXACT is the first FDA-approved selective APRIL inhibitor for adults with primary IgAN at risk of disease progression. The newly reported two-year results complete the Phase 3 VISIONARY dataset and support Otsuka’s ongoing rolling supplemental Biologics License Application (sBLA) seeking traditional FDA approval. A complete analysis of the study will be presented at an upcoming scientific congress.
What This Means
The Phase 3 VISIONARY trial represents a significant advance in the treatment of IgA nephropathy. Beyond reducing proteinuria, VOYXACT demonstrated sustained stabilization of kidney function over two years while maintaining a safety profile comparable to placebo.
By achieving the KDIGO therapeutic goal of slowing kidney function decline to the physiologic rate, the findings provide evidence that selective APRIL inhibition may modify the underlying course of IgAN. If the ongoing supplemental Biologics License Application is approved, VOYXACT could reshape the treatment paradigm for patients with progressive IgA nephropathy by offering an early targeted therapy that addresses a key immune driver of the disease.