ERA 2025: Sibeprenlimab Halves Proteinuria in IgAN in Phase 3 VISIONARY Trial

Use of sibeprenlimab was associated with a 51.2% reduction in proteinuria at 9 months relative to placebo therapy among patients with IgA nephropathy, according to an interim analysis of the phase 3 VISIONARY trial.

Presented at the 62nd European Renal Association (ERA 2025) Congress, the trial, which provided further insight into the effects of sibeprenlimab in this patient population beyond the announcement of topline results made in October 2024 by Otsuka Pharmaceutical.1,2,3

"The VISIONARY phase 3 interim analysis shows a robust proteinuria reduction of 51.2% in the group treated with sibeprenlimab relative to placebo. These results affirm our belief in the efficacy of sibeprenlimab in the largest phase 3 IgAN trial to date. The study enrolled a diverse patient population reflective of the disease epidemiology," said Dana Rizk, MD, professor of medicine in the division of nephrology at the University of Alabama at Birmingham.3 "The safety data emerging from VISIONARY is reassuring and adds to our existing knowledge about sibeprenlimab's safety profile from prior programs. This is very exciting news for patients and adds a therapeutic option with a novel mechanism of action potentially targeting the immunologic pathogenesis of IgAN."

Presented just more than 2 months after Otsuka Pharmaceutical announced a Biologics License Application (BLA) filing for sibeprenlimab, the VISIONARY trial, which was presented at the meeting as a late-breaking clinical trial, is billed as the largest clinical trial in IgAN to date, with 530 total participants. Less than 2 weeks prior to the presentation, the company announce date FDA had accepted and granted priority review for their BLA and the application has been given a target action date of November 28, 2025.1,2,3

Per trial protocol, patients were randomized in a 1:1 ratio to receive 400 mg sibeprenlimab subcutaneously wary 4 week or placebo therapy. Key inclusion criteria for the trial were having biopsy-confirmed IgAN, being at least 18 years old, a UPCR of 0.75 grams per gram or urine protein ex ration of 1 gram per day or more, an eGFR of 30 mL/min/1.73m2 or greater, and be receiving stable dose of RAASI with or without SGLT2 inhibitors for 3 or more months prior to enrollment.1

Although 530 patients were enrolled in the trial, the data presented at ERA 2025 included the first 320 patients randomized in the trial. This group included 152 patients randomized to sibeprenlimab and 168 randomized to placebo therapy.1

The primary endpoint of interest for the trial was the ratio of 24-hour urine protein-to-creatinine ratio (UPCR) at 9 months relative to baseline. The trial’s key secondary endpoint was the annualized slope of eGFR over 24 months, which Vlado Perkovic, MBBS, PhD, of the George Institute for Global Health, noted during his presentation at ERA 2025 will be available in a future presentation expected in 2026.1

Results indicated use of sibeprenlimab was associated with a 50.2% reduction in 24-hour UPCR at 9 months, which correlates to a placebo-adjusted treatment effect of 51.2% among the 320 patients included in the prespecified analysis. As part of the trial, investigators performed spot measurements of UPCR and these assessments revealed UPCR reductions in the sibeprenlimab group began as early as 4 weeks.1

Safety data from the analysis at ERA 2025 indicated treatment-emergent adverse events (TEAE) occurred among 76.3% of patients treated in the sibeprenlimab group relative to 84.5% in the placebo group. Additionally, investigators pointed out serious TEAEs occurred among 3.9% in the sibeprenlimab group compared to 5.4% in the placebo group.1

"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.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."

References:

1. Perkovic V. Sibeprenlimab for Patients With IgA Nephropathy: Results From a Prespecified Interim Analysis of the Phase 3 VISIONARY Study. Presented at: 62nd European Renal Association Congress. June 04 – 07, 2025. Vienna, Austria.

2. Otsuka Pharmaceutical Co. Otsuka Announces Positive Interim Results from the Phase 3 Trial of Sibeprenlimab for the Treatment of Immunoglobulin A Nephropathy in Adults｜News Releases | Otsuka Pharmaceutical Co., Ltd. Otsuka Pharmaceutical Co., Ltd. Published October 22, 2024. Accessed June 6, 2025. https://www.otsuka.co.jp/en/company/newsreleases/2024/20241022_1.html

3. Otsuka Pharmeutical 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