Sibeprenlimab (Voyxact) Stabilizes Kidney Function in IgAN

2-year results from the Phase 3 VISIONARY trial suggest that sibeprenlimab-szsi (Voyxact) returned the annualized rate of kidney function decline in IgA nephropathy (IgAN) to a near-physiologic level.

The data were presented in a late-breaking session at GlomCon Hawaii 2026 and announced by Otsuka Pharmaceutical Development & Commercialization, Inc., on August 3, 2026.¹

The trial met its key secondary endpoint, the annualized estimated glomerular filtration rate (eGFR) slope was +0.3 mL/min/1.73 m²/year (95% Confidence Interval [CI], -0.4 to 0.9) with sibeprenlimab, compared with -4.2 mL/min/1.73 m²/year (95% CI, -4.9 to -3.6) with placebo, a treatment difference of +4.5 mL/min/1.73 m²/year (95% CI, 3.6 to 5.4; P<.0001).¹

“The VISIONARY two-year eGFR results achieved the KDIGO treatment goal of reducing kidney function decline to near physiological level, fundamentally altering the disease progression,” said Dana Rizk, MD, professor of medicine in the division of nephrology at the University of Alabama at Birmingham and a VISIONARY site investigator, in Otsuka's press release.¹

Does Sibeprenlimab Slow eGFR Decline in IgA Nephropathy

VISIONARY (NCT05248646) is a global, randomized, double-blind, placebo-controlled trial enrolling adults with primary IgAN at risk for disease progression^.1

Its primary endpoint, proteinuria reduction at 9 months, previously supported the drug's November 2025 accelerated approval.3 The newly reported 24-month analysis adds the eGFR slope endpoint, calculated using a prespecified linear mixed-effects model of repeated measurements from week 4 through week 104.

A complementary measure, the least-squares mean change in eGFR from baseline, also favored sibeprenlimab, by 9.2 mL/min/1.73 m² (95% CI, 7.1 to 11.4; P<.0001).¹

Safety through 2 years was reported as consistent with placebo. Overall adverse events occurred in 90.7% of sibeprenlimab-treated patients versus 90.0% on placebo, infections in 51.4% versus 51.0%, and injection site reactions in 35.1% versus 32.2%.¹

Serious infections were less frequent with sibeprenlimab than placebo (1.9% vs 4.0%), and the company reported no new safety signals.1 A full analysis of the 2-year dataset is planned for a future scientific congress.¹

How Does Voyxact Fit Into the IgA Nephropathy Treatment Landscape

IgAN is a progressive, immune-mediated glomerular disease that typically presents in adults aged 20 to 40 years and can progress to kidney failure over a patient's lifetime.¹

The disease is driven in part by accumulation of galactose-deficient IgA1 (Gd-IgA1) immune complexes in the kidney. The KDIGO 2025 guideline defines effective disease control as reducing kidney function loss to below roughly 1 mL/min/1.73 m²/year, the estimated rate in adults without kidney disease.4

As of the drug's 2025 approval, sparsentan and budesonide were the only other agents with full FDA approval specifically for slowing kidney function loss in IgAN. That leaves a treatment gap that eGFR-stabilizing data could address if confirmed.

How Does Sibeprenlimab Work, and What Is Its Current FDA Approval Status

Sibeprenlimab is a humanized monoclonal antibody that selectively blocks A proliferation-inducing ligand (APRIL), an upstream driver of pathogenic Gd-IgA1 production implicated in IgAN's underlying immunopathology.^1,2 It is administered as a self-injected subcutaneous dose every 4 weeks.¹

The FDA granted sibeprenlimab accelerated approval on November 25, 2025, based on interim VISIONARY proteinuria data. That approval was explicitly conditioned on verification of long-term clinical benefit in a confirmatory analysis.³

Otsuka said in its release that the newly reported 2-year eGFR findings will be incorporated into a rolling supplemental biologics license application seeking traditional approval.¹

What's Needed Before Voyxact Gains Full FDA Approval

The current indication remains proteinuria reduction under accelerated approval. The company states it has not yet been established whether sibeprenlimab slows long-term kidney function decline, pending completion of the sBLA review.¹

An open-label extension study (NCT05248659) is ongoing to characterize durability of effect and long-term safety beyond 2 years.¹

References

1. Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka unveils unprecedented Phase 3 VISIONARY two-year eGFR results demonstrating VOYXACT (sibeprenlimab-szsi) stabilizes kidney function decline to baseline physiologic rate in IgA nephropathy (IgAN). News release. August 3, 2026.

2. Perkovic V, Trimarchi H, Tesar V, et al. Sibeprenlimab in IgA nephropathy — interim analysis of a phase 3 trial. N Engl J Med. 2026;394(7):635-646. doi:10.1056/NEJMoa2512133

3. FDA approves new treatment for primary immunoglobulin A nephropathy. News release. FDA. November 25, 2025. Accessed August 4, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-treatment-primary-immunoglobulin-nephropathy

4. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group. KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). Kidney Int. 2025;108(4S):S1-S71.