Otsuka’s Phase III VISIONARY trial interim results show VOYXACT® (sibeprenlimab‑szsi) slowed kidney function decline in IgA nephropathy, reinforcing selective APRIL inhibition as a targeted therapy and supporting FDA review for traditional approval.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Otsuka presented interim Phase III VISIONARY (NCT05248646) data at the European Renal Association (ERA) Congress 2026 showing that VOYXACT® (sibeprenlimab‑szsi) preserved kidney function in adults with primary IgA nephropathy (IgAN) at risk of progression. IgAN is a leading cause of chronic kidney disease and kidney failure worldwide.
The interim analysis included 320 patients globally, with 152 receiving sibeprenlimab and 168 placebo. After 12 months, VOYXACT patients showed a mean increase in eGFR of +0.7 mL/min/1.73 m² versus a decline of ‑4.8 mL/min/1.73 m² in the placebo group, yielding a treatment effect of 5.5 mL/min/1.73 m².
eGFR Slope and Clinical Relevance
Annualized eGFR slope analysis showed a decline of ‑3.0 mL/min/1.73 m² per year with sibeprenlimab compared with ‑7.6 mL/min/1.73 m² per year for placebo, representing a treatment effect of 4.6 mL/min/1.73 m² per year.
Investigators noted that sibeprenlimab slowed kidney function decline compared with placebo, approaching the kidney disease: Improving Global Outcomes (KDIGO) target of limiting annual loss to below 1 mL/min/1.73 m². These findings suggest selective APRIL inhibition may help preserve long‑term kidney function in IgAN.
Mechanism of Action
VOYXACT is the first and only FDA‑approved selective APRIL (A Proliferation‑Inducing Ligand) inhibitor for IgAN. APRIL drives production of pathogenic IgA, a central contributor to kidney inflammation and progressive damage. By selectively inhibiting APRIL while sparing B cells, VOYXACT reduces pathogenic IgA production without broad immunosuppression, differentiating it from other immune‑modulating strategies.
Safety Profile and Broader Clinical Impact
The therapy was generally well tolerated, with a safety profile comparable to placebo. The most common adverse events were infections and injection‑site reactions, while overall event rates were similar between treatment groups.
Interim findings also build on previously reported reductions in galactose‑deficient IgA1 (Gd‑IgA1), proteinuria, and hematuria, strengthening evidence that APRIL inhibition preserves kidney function and improves disease control.
Together, these data support the hypothesis that targeting upstream mechanisms can deliver meaningful long‑term benefits for patients with IgAN.
Expert Perspectives and Regulatory Pathway
Clinical experts emphasized the importance of slowing kidney function decline to reduce the risk of kidney failure, dialysis, and transplantation.
Vlado Perkovic, MBBS, PhD, Provost at the University of New South Wales, noted that selective APRIL inhibition may help preserve kidney function and improve long‑term outcomes.
John Kraus, M.D., Ph.D., Executive Vice President and Chief Medical Officer at Otsuka, said the new eGFR findings complement earlier biomarker reductions and reinforce VOYXACT’s differentiated mechanism and favorable benefit‑risk profile.
Otsuka has initiated a rolling submission of a supplemental Biologics License Application (sBLA) to the U.S. FDA seeking traditional approval based on 24‑month eGFR endpoint data. Full results from the final Phase III VISIONARY analysis are expected at a future medical meeting and will be pivotal for regulatory review and potential global submissions.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.