FDA Accelerates Approval of Otsuka’s VOYXACT® (sibeprenlimab-szsi) for IgA Nephropathy

Otsuka Pharmaceutical has received FDA accelerated approval for VOYXACT® (Sibeprenlimab-szsi), a first-in-class therapy to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. This breakthrough makes VOYXACT the only approved APRIL-inhibiting antibody for IgAN, offering a new targeted approach for patients facing this chronic, immune-mediated kidney disease.

The VISIONARY study (NCT05248646) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in approximately 530 adults (510 main cohort, 20 exploratory) with biopsy-confirmed primary IgA nephropathy (IgAN). Participants were randomized to receive either sibeprenlimab 400 mg subcutaneously every 4 weeks or placebo, alongside maximally tolerated standard-of-care including ACE inhibitors/ARBs and possibly SGLT2 inhibitors.

The primary endpoint is the relative change from baseline in 24-hour urinary protein to creatinine ratio (uPCR) after 9 months of treatment. Key secondary endpoints include the annualized slope of estimated glomerular filtration rate (eGFR) over approximately 24 months and the proportion of patients achieving specific proteinuria reductions at 12 months. The trial evaluates the effect of Sibeprenlimab on proteinuria and kidney function progression in IgAN patients.

At 9 months, patients receiving Sibeprenlimab had about a 50% reduction in 24‑hour urine protein (uPCR), while the placebo group showed about a 2% increase, giving a placebo‑adjusted reduction of roughly 51% with Sibeprenlimab and consistent benefit across all analyzed subgroups. At 12 months, Sibeprenlimab produced a 56.6% reduction in uPCR‑24h versus 5.1% with placebo, corresponding to a 54.3% placebo‑adjusted reduction and was also associated with lower levels of immunoglobulins, APRIL, Gd‑IgA1, hematuria, and higher rates of proteinuric remission compared with placebo.

The safety profile was favorable and consistent with placebo. At the interim analysis cutoff, treatment-emergent adverse events occurred in 74.1% of patients receiving Sibeprenlimab and 82.1% of those receiving placebo, with most events being mild to moderate in severity. The most common adverse events included upper respiratory tract infections (14.7% with Sibeprenlimab vs. 13.9% placebo) and nasopharyngitis (12.4% vs. 10.0%). Injection site reactions were reported but were mostly mild. Overall, the safety observations support sibeprenlimab’s tolerability in adults with IgA nephropathy. The trial continues to collect long-term safety data as the study progresses toward completion.

Voyxact is a humanized monoclonal antibody administered as 400 mg single subcutaneous (SC) injection every 4 weeks, administered via prefilled syringe for self-administration after training. Voyxact selectively binds and inhibits APRIL (A-Proliferation-Inducing Ligand), a cytokine that drives IgAN pathology by promoting galactose-deficient IgA1 (Gd-IgA1) production and autoantibody formation. This blockade reduces pathogenic IgA immune complexes, addressing the root cause of glomerular inflammation and injury in IgAN.

IgA nephropathy affects adults typically between 20 and 40 years old, often leading to end-stage kidney disease over a patient’s lifetime. Despite current standard-of-care therapies such as ACE inhibitors, ARBs, and SGLT2 inhibitors, there remains a significant unmet need for disease-targeted treatments.

John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka, stated: “VOYXACT offers a novel targeted approach with strong efficacy, safety, and once-every-four-weeks dosing for IgAN patients.”​

Dr. Dana Rizk, professor of medicine at the University of Alabama at Birmingham and VISIONARY study investigator said “VOYXACT is the first approved APRIL-blocking treatment for adults with primary IgAN at risk of progression.”​ He also added “I’m encouraged by its potential to help improve the outlook for IgAN patients.”

Bonnie and Ed Schneider, IgA Nephropathy Foundation co-founders, stated: “We’re thrilled about VOYXACT’s accelerated approval as a new option for IgAN patients.”​

VOYXACT’s FDA approval is contingent on proteinuria reduction as a surrogate marker. The ongoing phase 3 VISIONARY trial will evaluate whether the drug slows the decline in kidney function (as measured by eGFR) over 24 months. Results are expected in early 2026 and may support full traditional approval.