Otsuka’s VOYXACT reduced kidney outcome risk by 97.1% in the Phase 3 VISIONARY trial, with sustained kidney function preservation over two years in IgAN.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Otsuka’s VOYXACT (sibeprenlimab-szsi) preserved kidney function over two years in adults with immunoglobulin A nephropathy (IgAN), reducing the risk of a composite kidney outcome by 97.1% versus placebo. Final results from the Phase 3 VISIONARY trial support the therapy’s potential as a disease-modifying treatment and will inform Otsuka’s application for traditional US FDA approval.
VISIONARY Demonstrates Sustained Kidney Protection
The global, randomized, double-blind, placebo-controlled Phase 3 VISIONARY trial (NCT05248646) enrolled 510 adults with primary IgAN at risk of disease progression. Over two years, the composite kidney outcome occurred in one of 259 patients receiving VOYXACT (0.4%), compared with 28 of 251 patients receiving placebo (11.2%), representing a 97.1% lower hazard of the outcome.
The composite included sustained estimated glomerular filtration rate (eGFR) decline of at least 40%, sustained doubling of serum creatinine, or sustained eGFR below 15 mL/min/1.73 m². Individual outcomes also favored VOYXACT. Sustained eGFR decline of at least 40% occurred in one treated patient versus 28 placebo recipients, while sustained doubling of serum creatinine occurred in no treated patients versus 13 placebo recipients. Sustained eGFR below 15 mL/min/1.73 m² occurred in one patient receiving VOYXACT versus 10 receiving placebo. No patients in the VOYXACT group-initiated kidney replacement therapy, compared with five in the placebo group.
The findings were presented at the American Society of Nephrology Kidney Week 2026 and published simultaneously in The New England Journal of Medicine on October 22, 2026.
eGFR and Proteinuria Results Support Disease Modification
VOYXACT also demonstrated a sustained effect on kidney function. The annualized eGFR slope was +0.3 mL/min/1.73 m²/year with sibeprenlimab versus −4.2 mL/min/1.73 m²/year with placebo. The between-group difference was 4.5 mL/min/1.73 m²/year (95% CI, 3.6–5.4; p<0.0001).
At month 24, the least-squares mean change in eGFR from baseline was +1.3 mL/min/1.73 m² in the VOYXACT group, compared with −7.9 mL/min/1.73 m² in the placebo group. The between-group difference was 9.2 mL/min/1.73 m² (95% CI, 7.1–11.4; p<0.0001).
Treatment also reduced proteinuria, a marker of kidney damage. The 24-hour urine protein-to-creatinine ratio declined by 61.3% from baseline at month 24. Among patients with hematuria at baseline, 78.6% receiving VOYXACT achieved a negative urine dipstick result, compared with 20.2% receiving placebo.
The eGFR findings are consistent with the 2025 kidney disease: Improving Global Outcomes (KDIGO) treatment goal of slowing kidney function decline toward near-physiologic rates, generally below 1 mL/min/1.73 m²/year for most adults. However, these are group-level results and do not mean that every patient will maintain or improve kidney function.
Selective APRIL Inhibition Targets IgAN Pathogenesis
IgAN is a progressive, immune-mediated kidney disease characterized by the accumulation of immune complexes containing galactose-deficient immunoglobulin A1 (Gd-IgA1). These complexes contribute to inflammation and kidney damage, potentially leading to kidney failure.
VOYXACT is a humanized monoclonal antibody that binds to and inhibits A PRIL (a proliferation-inducing ligand), a protein involved in B-cell activity and the production of immunoglobulins, including pathogenic Gd-IgA1. By reducing APRIL activity, sibeprenlimab lowers circulating Gd-IgA1 levels and targets an important driver of IgAN rather than broadly suppressing the immune system.
The consistency of the kidney function, proteinuria, and composite outcome findings strengthens the evidence for selective APRIL inhibition as a potential disease-modifying approach.
Two-Year Safety Profile Remains Comparable to Placebo
VOYXACT’s overall safety profile remained consistent through two years. 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%.
Serious infections were reported in 1.9% of VOYXACT-treated patients versus 4.0% of placebo recipients. The company reported no new safety signals, with serious and severe adverse events and treatment discontinuations also lower in the treatment group.
Dana Rizk, a VISIONARY investigator and professor of medicine in the Division of Nephrology at the University of Alabama at Birmingham, said the magnitude and consistency of the kidney function findings provide important evidence for the potential role of sibeprenlimab in changing the long-term course of IgAN.
Otsuka Advances Application for Traditional FDA Approval
The US FDA granted VOYXACT accelerated approval on November 25, 2025, for adults with primary IgAN at risk of disease progression. Otsuka has completed the rolling submission of a supplemental Biologics License Application (sBLA) seeking traditional approval. The submission includes the two-year eGFR findings from VISIONARY.
VOYXACT is administered as a self-injected subcutaneous dose once every four weeks. Further evidence will come from the long-term extension study (NCT05248659), which will assess outcomes beyond the controlled two-year trial period.
Otsuka has also initiated a Phase 3 open-label study (NCT07770815) evaluating sibeprenlimab in children aged 2–17 years with IgAN as an addition to standard-of-care therapy. A separate Phase 2 open-label study (NCT07861113) is evaluating the therapy in primary membranous nephropathy, immune-mediated focal segmental glomerulosclerosis, and minimal change disease.
The two-year VISIONARY results strengthen the clinical case for APRIL inhibition in IgAN. The pending regulatory review and longer-term follow-up will help determine how these findings translate into routine clinical practice.
Reference
Otsuka Presents Landmark Final Phase 3 VISIONARY Results at ASN Demonstrating VOYXACT® (sibeprenlimab-szsi) Stabilized Kidney Function and Reduced Risk of Disease Progression and Kidney Failure, Redefining Treatment Paradigm in IgA Nephropathy, Otsuka, 22 October 2026
Trial of Sibeprenlimab in the Treatment of A Nephropathy (IgAN), ClinicalTrials.gov ID NCT05248646
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.