PRINCETON, N.J. & TOKYO — The U.S. Food and Drug Administration has granted accelerated approval for Otsuka’s VOYXACT (sibeprenlimab-szsi), authorizing the drug for reducing proteinuria in adults with primary immunoglobulin A nephropathy, a chronic kidney disease that can progress to kidney failure. The approval makes VOYXACT the first therapy targeting APRIL, a protein involved in the underlying biology of IgA nephropathy.
The decision is based on interim results from the Phase 3 VISIONARY trial, where VOYXACT reduced proteinuria by 50 percent at nine months compared with a 2 percent reduction in the placebo group. The placebo-adjusted treatment effect was 51 percent, with results reaching statistical significance (P<0.0001) among 320 participants.
Proteinuria reduction has been widely used as a surrogate endpoint in IgA nephropathy trials and is considered a predictor of delayed progression to kidney failure. However, it has not yet been established whether VOYXACT slows long-term kidney function decline. Full approval will depend on confirmatory data from the ongoing VISIONARY study, which is measuring changes in estimated glomerular filtration rate over two years. Those results are expected in early 2026.
VOYXACT is administered as a self-injected subcutaneous dose once every four weeks. In the study, the most common adverse reactions, occurring in at least 10 percent of patients and at a higher rate than placebo, were infections (49 percent vs. 45 percent) and injection-site reactions (24 percent vs. 23 percent).
The drug works by blocking APRIL, or A-Proliferation-Inducing Ligand, which promotes production of galactose-deficient IgA1, a molecule implicated in the pathogenesis of IgA nephropathy. By inhibiting APRIL, VOYXACT reduces circulating levels of this pathogenic IgA subtype.
Otsuka executives said the approval offers a new targeted option for patients who have had limited choices. “The availability of VOYXACT represents a novel targeted approach to help manage this complex disease for patients living with IgAN,” said John Kraus, M.D., Ph.D., the company’s chief medical officer. Kraus said the once-monthly dosing and safety profile could make the therapy an appealing alternative.
Dana Rizk, M.D., a nephrologist at the University of Alabama at Birmingham and an investigator in the VISIONARY trial, said the APRIL-blocking mechanism represents a new therapeutic pathway for affected patients. “VOYXACT is the first approved treatment for adults with primary IgAN at risk for disease progression that blocks the activity of APRIL,” she said.
Patient advocacy groups also welcomed the approval. Bonnie and Ed Schneider, co-founders of the IgA Nephropathy Foundation, said new options are urgently needed for patients who often progress to end-stage kidney disease despite current standards of care.
The FDA’s decision marks another step in the growing use of biomarker-based accelerated approvals for kidney diseases, which increasingly rely on proteinuria as a surrogate endpoint while longer-term outcomes continue to be studied.
