Voyxact Lands FDA Accelerated Approval Following Positive Results in Phase III VISIONARY Trial

Otsuka’s Voyxact (sibeprenlimab-szsi) has been granted accelerated approval by the FDA for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.¹

The approval is backed by data from an interim analysis of the Phase III VISIONARY clinical trial (NCT05248646), which demonstrated significant improvements in proteinuria reduction.

In a company press release, Dana Rizk, MD, professor of medicine in the division of nephrology at the University of Alabama at Birmingham and Voyxact VISIONARY study investigator and co-chair of the steering committee, said: “Voyxact is the first approved treatment for adults with primary IgAN at risk for disease progression that blocks the activity of A-PRoliferation-Inducing-Ligand (APRIL). I'm encouraged by its potential to help improve the outlook for IgAN patients.”

Voyxcat demonstrates significant proteinuria reduction in VISIONARY trial

Results from the VISIONARY study were shared by Otsuka earlier in June. When compared to placebo, Voyxact achieved a statistically significant and clinically meaningful 51.2% (P<0.0001) reduction in proteinuria at nine months.²

Additional findings from the Phase III trial include:

• Adverse reactions occurring in ≥10% of participants and at higher rates with Voyxact than placebo included infections (49% vs 45%) and injection-site reactions (24% vs 23%).
• Upper respiratory infection was the most frequent infection (15% vs 14%), and injection-site erythema was the most common local reaction (13% vs 12%).
• Most adverse events were mild or moderate and resolved without treatment interruption or discontinuation.

In a statement from the time of when the results were shared, Rizk said: “The VISIONARY Phase III interim analysis shows a robust proteinuria reduction of 51.2% in the group treated with sibeprenlimab relative to placebo. These results affirm our belief in the efficacy of sibeprenlimab in the largest Phase III IgAN trial to date. The study enrolled a diverse patient population reflective of the disease epidemiology. The safety data emerging from VISIONARY is reassuring and adds to our existing knowledge about sibeprenlimab’s safety profile from prior programs. This is very exciting news for patients and adds a therapeutic option with a novel mechanism of action potentially targeting the immunologic pathogenesis of IgAN.”

Future research in kidney function

While Voyxact’s approval is based on the reduction of proteinuria, Otsuka says it is currently unknown how the humanized monoclonal antibody slows kidney function decline over the long-term in IgAN patients. The company is awaiting results from a confirmatory study within VISIONARY investigating whether Voyxcat slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline at 24 months.

VISIONARY trial design

The VISIONARY trial is a multicenter, randomized, double-blind, placebo-controlled study enrolling 510 adults with biopsy-confirmed IgAN on maximally tolerated ACEi/ARB ± SGLT2 inhibitor therapy.

• Key inclusion criteria included urine protein-to-creatinine ratio (uPCR) ≥0.75 g/g or ≥1 g/day, eGFR ≥30 mL/min/1.73 m², and stable supportive therapy for ≥3 months before screening.
• Participants were randomized to receive subcutaneous sibeprenlimab 400 mg every four weeks or placebo, continuing background therapy throughout the study.
• The primary endpoint is percent change in 24-hour uPCR at month nine versus baseline.
• Following the interim analysis (n=320) showing a 51% placebo-adjusted reduction in proteinuria, the full study continues with eGFR slope results expected in 2026.

“The availability of Voyxact represents a novel targeted approach to help manage this complex disease for patients living with IgAN. With its targeted mechanism, strong efficacy, safety profile, and once-every-four-weeks dosing, Voyxact offers a new option for IgAN patients. We recognize the urgent need for new treatment options for IgAN and are thankful for the patients and healthcare professionals who continue to participate in our clinical trial program,” said John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka, in a company statement.

References

1. Otsuka Receives FDA Accelerated Approval for VOYXACT® (sibeprenlimab-szsi) for the Reduction of Proteinuria in Adults with Primary Immunoglobulin A Nephropathy (IgAN) at Risk for Disease Progression. News release. Otsuka. November 25, 2025. Accessed December 1, 2025. https://www.otsuka-us.com/news/otsuka-receives-fda-accelerated-approval-voyxactr-sibeprenlimab-szsi-reduction-proteinuria

2. Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN). News release. Otsuka. June 6, 2025. Accessed December 1, 2025. https://www.otsuka-us.com/news/otsuka-sibeprenlimab-phase-3-data-show-statistically-significant-and-clinically-meaningful