FDA Awards Accelerated Approval to Sibeprenlimab in IgA Nephropathy

The US Food and Drug Administration (FDA) has approved sibeprenlimab (Voyxact) for reducing proteinuria in primary IgA nephropathy (IgAN) in adults at risk for disease progression, according to a November 25, 2025 update on the agency website. 1

A targeted APRIL inhibitor from Otsuka Pharmaceutical Co., sibeprenlimab was examined in the VISIONARY trial, which is billed by Otsuka as the largest phase 3 trial ever conducted in IgAN, where use was associated with a 54.3% placebo-adjusted reduction in geometric mean 24-hour urine protein-to-creatinine ratio (UPCR) from baseline after 12 months of treatment.2

"We are confident about the potential of sibeprenlimab and are grateful to the patients who are helping to further the science by participating in these important trials," said John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc, in a June 2025 press release around the presentation of interim UPCR data.3 "Proteinuria control is an important independent predictor for long-term prognosis, and this interim data reinforces our belief that selectively targeting APRIL has the potential to be an effective and safe approach for this progressive and irreversible kidney disease."

The accelerated approval of sibeprenlimab is the latest in a series of regulatory decisions in recent years for IgAN, following accelerated approvals for iptacopan (Fabhalta) in August 2024 and atrasentan (Vanrafia) in April 2025. As of November 2025, sparsentan (Filspari) and budesonide (Tarpeyo) are the only agents to receive full FDA approval to reduce the loss of kidney function in adults with IgAN.4

Spanning 31 countries, the VISIONARY trial randomized 510 participants in a 1:1 ratio to sibeprenlimab or placebo therapy for 2 years. According to data from the 62nd European Renal Association (ERA 2025) Congress presentation, 98% of participants were on renin-angiotensin system inhibitors and 39% were also taking SGLT2 inhibitors at baseline.2,3

The 12-month data from the trial, which was presented at the American Society of Nephrology (ASN) Kidney Week 2025, a indicated use was associated with a reduction in24-hour UPCR of 56.6% (95% Confidence Interval [CI], 50.8% to 61.7%) compared with 5.1% (-6.7% to 15.7%) for placebo, yielding a between-group difference of 54.3% (95% CI, 46.4% to 60.9%).2

Additional data presented at ASN Kidney Week 2025 indicated sibeprenlimab use was associated with consistent reductions in 24-hour across all evaluated subgroups, including ethnicity, sex at birth, age, race, and SGLT2 inhibitor use at baseline. The largest effects were observed in patients with higher baseline proteinuria (UPCR > 2.0 g/g: 64.7%).2

The 12-month data also pointed to reductions in spot UPCR of 51.1% with sibeprenlimab compared to -8.5% with placebo and proteinuric remission (<0.5 g/d) at month 12 occurred in 34.3% of sibeprenlimab-treated patients compared to 12.7% with placebo. Investigators also noted 48-week biomarker reductions in IgA (68.8% vs 23.6%), IgG (35.0% vs 4.6%), IgM (74.5% vs 1.9%), APRIL (95.8% vs 25.5%), and Gd-IgA1 (67.1% vs 1.2%) favored sibeprenlimab over placebo.2

The full 2-year results, which will include eGFR, are expected to be released in 2026.3

“This is the proteinuria data. It's incredibly promising. The phase 2 GFR data looks, if anything, even more promising, but we need to wait now for the remaining eGFR and other outcome data at 2 years of follow-up,” remarked Perkovic, in an episode of Kidney Compass at ERA 2025.

References:

1. US Food and Drug Administration. Novel Drug Approvals for 2025. U.S. Food and Drug Administration. Published November 25, 2025. Accessed November 25, 2025. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025.

2. Perkovic V, Barratt J, Lafayette RA, et al. Sibeprenlimab for the Treatment of IgAN: VISIONARY Phase 3 Interim and Prespecified Subgroup Analyses. Presented at: ASN Kidney Week. Houston, Texas. November 05-09, 2025.

3. Otsuka Pharmaceutical Co. Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN)｜News Releases | Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Published June 6, 2025. Accessed June 6, 2025. https://www.otsuka.co.jp/en/company/newsreleases/2025/20250606_1.html.

4. Roberts L, Jones M, Barratt J, Selvaskandan H. IgA nephropathy: a paradigm shift in treatment strategies. Curr Opin Nephrol Hypertens. 2025;34(5):381-388. doi:10.1097/MNH.0000000000001105