Sibeprenlimab Safely Reduces Gd-IgA1, Other IgAN Markers, in New Analysis

Sibeprenlimab has continued to demonstrate its benefit and continued safety in people with IgA nephropathy (IgAN), including reducing galactose-deficient immunoglobulin A1 (Gd-IgA1).1

New data on sibeprenlimab, a targeted APRIL inhibitor, from a prespecified interim analysis of the VISIONARY trial, were presented by Vlado Perkovic, MBBS, PhD, dean and scientia professor of medicine, University of New South Wales, Sydney, New South Wales, Australia, at the American Society of Nephrology (ASN) Kidney Week 2025, held November 5-9, 2025, in Houston, Texas.

VISIONARY (NCT05248646), a phase 3 double-blind, placebo-controlled trial spanning 31 countries, was billed as the largest phase 3 trial ever conducted in IgAN. The trial randomized 510 adults with IgAN on supportive therapy 1:1 to subcutaneous sibeprenlimab 400 mg or placebo Q4W. Investigators assessed uPCR-24h reduction and remission, hematuria, serum immunoglobulins, APRIL, Gd-IgA1, and safety for up to 12 months. They further assessed urine protein-to-creatinine ratio (UPCR)-24h responses across subgroups, stratifying for demographics, screening uPCR-24h, eGFR, SGLT2i use, and prior immunosuppression.

A previous interim analysis presented by Perkovic at the 62nd European Renal Association (ERA 2025) Congress demonstrated that sibeprenlimab achieved a significant 50.2% reduction in geometric mean 24-hour uPCR from baseline after 9 months of treatment while the placebo group saw a slight increase of 2.1%, yielding a between-group difference of 51.2% (96.5% CI, 42.9% to 58.2%; P <.0001).2

Perkovic joined Kidney Compass hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS for a special edition episode during ERA 2025 to discuss the data and its implications, which you can watch here.

“This is another look at the proteinuria data, looking at the proteinuria response across different baseline characteristics, but also looking at other biomarkers of improved glomerular health, so the impact on hematuria, the impact on Gd-IgA1, which has not previously been discussed,” Jonathan Barratt, MBChB, PhD, Mayer Professor of Renal Medicine, University of Leicester, told HCPLive about the new analysis.

Importantly, 98% of participants were on renin-angiotensin system inhibitors and 39% were also taking SGLT2 inhibitors at baseline, suggesting that sibeprenlimab delivered a significant additional benefit beyond optimized standard of care.2

In this new analysis, Perkovic and colleagues found that those treated with sibeprenlimab had greater reductions in uPCR-24h (54.3% placebo-adjusted) and spot uPCR at 12 months with sibeprenlimab compared to placebo. Furthermore, sibeprenlimab substantially reduced serum immunoglobulins, Gd-IgA1, APRIL, and rates of hematuria, as well as yielding higher rates of proteinuric remission (34.3%) compared to placebo (12.7%).1

“These data give us a fuller picture of where we are with this drug while we're all desperately waiting to seek the glomerular filtration rate (GFR) data… Where we are, we can't see the GFR data. At the moment, it will be around in 2026 and again, the phase 2 data looked incredibly promising over that initial 12 month treatment period when sibeprenlimab was given,” Barratt said.

After 9 months of follow-up, uPCR-24h reduction was consistent across subgroups, including SGLT2i use. Safety profiles were comparable between groups and there were no deaths occurred. VISIONARY is ongoing, with efficacy and safety analyses of sibeprenlimab continuing for 24 months of follow-up.1 Otsuka Pharmaceutical also recently announced the US Food and Drug Administration had granted priority review for their BLA and the application has been given a target action date of November 28, 2025.3

“If we can truly arrest loss of kidney function in patients with IGA nephropathy, it will transform the outlook of these young people living with what at the moment is a relentlessly progressive kidney disease.”

References

1. 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. #SA-OR086

2. 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.

3. 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