Interim Phase 3 VISIONARY Data Show Sibeprenlimab Preserved Kidney Function in IgA Nephropathy

Interim results from the phase 3 VISIONARY trial showed sibeprenlimab-szsi (VOYXACT), a selective APRIL inhibitor, was associated with preserved kidney function over 12 months in adults with primary IgA nephropathy (IgAN) at risk for disease progression, according to findings presented at the European Renal Association (ERA) Congress 2026 in Glasgow.¹

In a pre-specified interim analysis of 320 patients, with 152 receiving sibeprenlimab and 168 receiving placebo, the mean estimated glomerular filtration rate (eGFR) increased 0.7 mL/min/1.73 m² (95% Confidence Interval [CI], -0.9 to 2.3) from baseline with sibeprenlimab, compared with a decline of 4.8 mL/min/1.73 m² (95% CI, -6.3 to -3.3) with placebo, representing a treatment effect of 5.5 mL/min/1.73 m² (95% CI, 3.4 to 7.6).¹

"The magnitude of the benefits were a surprise to me. We saw such a profound protection of kidney function in the sibeprenlimab-treated patients compared with those on placebo that suggests we can completely transform the trajectory of kidney function in these patients moving forward," said Vlado Perkovic, MBBS, PhD, provost at the University of New South Wales, Australia, and a VISIONARY investigator, in an interview with HCPLive.

What the Phase 3 VISIONARY Interim Data Showed

VISIONARY is an ongoing global phase 3 trial evaluating sibeprenlimab in adults with primary IgAN at risk for progression. The trial previously demonstrated a 51% reduction in proteinuria at 9 months with sibeprenlimab, supporting the potential role of APRIL inhibition as a disease-modifying approach in IgAN.

The current interim analysis evaluated kidney function outcomes over 12 months. A key secondary endpoint showed an annualized eGFR slope of -3.0 mL/min/1.73 m²/year (95% CI, -4.6 to -1.4) with sibeprenlimab compared with -7.6 mL/min/1.73 m²/year (95% CI, -9.1 to -6.1) with placebo, corresponding to a treatment effect of 4.6 mL/min/1.73 m²/year (95% CI, 2.5 to 6.8).¹

Perkovic noted that the placebo arm represented a high-risk population with rapidly progressive disease, while patients receiving sibeprenlimab experienced substantially slower kidney function decline. He said the magnitude of kidney protection observed exceeded expectations based on prior proteinuria findings.

According to Otsuka Pharmaceutical, the 12-month sibeprenlimab result meets the Kidney Disease: Improving Global Outcomes (KDIGO) benchmark for reducing annual eGFR decline to a normal physiologic rate of less than 1 mL/min/1.73 m² per year.¹

The trial will continue through the planned 24-month treatment period, with additional follow-up planned in an open-label extension study (NCT05248659).¹

Safety Findings Reported With Sibeprenlimab

Safety findings were generally comparable between treatment groups.¹ Infections occurred in 49% of patients receiving sibeprenlimab and 45% receiving placebo, while injection-site reactions occurred in 24% and 23%, respectively.¹

The most common infection was upper respiratory infection (15% vs 14%), and the most common injection-site reaction was erythema (13% vs 12%). Most adverse events were mild to moderate and resolved without treatment interruption.¹

Because sibeprenlimab reduces APRIL-mediated B-cell activity and immunoglobulin production, longer-term follow-up will be important to assess whether the safety profile remains consistent over 24 months.

Sibeprenlimab Mechanism and Regulatory History

Sibeprenlimab is a humanized monoclonal antibody that selectively binds APRIL, a cytokine involved in B-cell activation and production of pathogenic galactose-deficient IgA1 (Gd-IgA1), an upstream driver of IgAN.¹

Sibeprenlimab received FDA accelerated approval on November 25, 2025, for reducing proteinuria in adults with primary IgAN at risk for progression. Whether the therapy slows long-term kidney function decline has not yet been established.¹

The treatment is self-administered subcutaneously every 4 weeks. Otsuka has initiated a rolling supplemental Biologics License Application (sBLA) seeking traditional approval based on the VISIONARY trial's 24-month eGFR endpoint, which has not yet been reported.¹

Earlier phase 2 findings supporting selective APRIL inhibition were published in the New England Journal of Medicine.²

Disease Burden and Next Steps

IgAN is a chronic immune-mediated glomerular disease characterized by deposition of Gd-IgA1 immune complexes that drive progressive kidney injury.¹˒³ Although supportive care can slow progression, many patients continue to experience kidney function decline and may progress to kidney failure, highlighting the need for therapies targeting upstream disease mechanisms.

Perkovic emphasized that the ongoing 24-month analysis will be critical for confirming whether the observed kidney function benefit is sustained and for further evaluating long-term safety.

"The 24-month data is still going to be very important, and we're going to look to that to confirm these findings, and also to tell us more about the safety of these agents," Perkovic said.

Because VOYXACT's current indication is based on proteinuria reduction under accelerated approval, confirmation of clinical benefit through longer-term kidney outcomes will be necessary to support traditional approval.¹

Editor’s Note: Relevant disclosures for Perkovic include Boehringer Ingelheim, AbbVie, Inc., Bristol-Myers Squibb, Servier, Astellas Pharma US, Merck, Janssen Pharmaceuticals, GSK, and others.

References

1. V. Perkovic, H. Trimarchi, V. Tesar, R. Lafayette, M.G. Wong, J. Barratt, Y. Suzuki, A. Liew, H. Zhang, K. Carroll, V. Jha, A. Quevedo, S.H. Han, M. Praga, B. Chacko, M. Sahay, C.K. Cheung, L. Kooienga, M. Walsh, J. Xia, C. Fajardo, L. Shah, J. Hafkin, and D.V. Rizk. Sibeprenlimab in IgA Nephropathy — Interim Analysis of a Phase 3 Trial. The New England Journal of Medicine. 2025. Nejm.org. 

2. Otsuka Pharmaceutical Development & Commercialization, Inc. Otsuka presents positive interim phase 3 VISIONARY eGFR data showing VOYXACT preserved kidney function over 12 months in IgA nephropathy. Press release. June 2026. Accessed July 8, 2026.

3. Mathur M, Barratt J, Chacko B, et al. A phase 2 trial of sibeprenlimab in immunoglobulin A nephropathy. N Engl J Med. 2023;389(12):1111-1121. doi:10.1056/NEJMoa2305635.