IgA nephropathy is a common and progressive autoimmune disease, and an important cause of chronic kidney disease and kidney failure. There is currently no cure and despite receiving supportive care, many patients remain at risk of progressing to kidney failure within 10 to 15 years. However, new data show that treatment with sibeprenlimab, an investigational monoclonal antibody, reduced proteinuria and biomarkers of IgA nephropathy and led to higher rates of hematuric/proteinuric remission for up to 12 months.
“The incidence is reported as 2.5 per 100,000 but I think that's a significant underestimate,” said study author Vlado Perkovic, MD, of the University of New South Wales, Sydney, and who presented the results at Kidney Week 2025. “It also affects young people, it affects them in the prime of their life, and is a slowly progressive condition over the course of their life. Finding a treatment that can reduce that risk and do that in the long term, is very important.”
The APRIL (A PRoliferation-Inducing Ligand) cytokine is a key driver of IgA neuropathy pathogenesis and promotes the production of pathogenic galactose-deficient(Gd) IgA1. However, current pharmacological treatments provide supportive care by addressing the generic drivers of the disease but do not target the specific underlying immune drivers. Sibeprenlimab selectively inhibits the activity of APRIL, and by selectively binding and inhibiting this cytokine, it reduces the both IgA and Gd-IgA1 levels.
The VISIONARY trial is an ongoing phase 3 placebo-controlled clinical trial that is evaluating the efficacy and safety of sibeprenlimab in adults with IgA nephropathy. The study’s primary endpoint is to compare the relative change in the urinary protein to creatinine ratio (uPCR) in a 24-hour urine collections at 9 months relative to baseline. Dr. Perkovic reported the results from a prespecified interim analysis.
The cohort was recruited from around the world, and included participants from 31 countries and 240 sites, A total of 530 patients with IgA neuropathy were randomly assigned to receive 400 mg sibeprenlimab or placebo, and the interim analysis reported results on the first 320 patients who were randomized in the trial: 152 patients in the sibeprenlimab arm and 168 in the placebo group.
Dr. Perkovic first presented the 9 month results which had previously been reported a few months earlier. Those results showed that use of sibeprenlimab was associated with a 50.2% reduction in 24-hour UPCR at 9 months, which correlated to a placebo-adjusted treatment effect of 51.2%. The level of protein in the urine was reduced by more than half, which was considered to be a very large effect.
The patients have now been followed out to 12 months, and he next presented the updated results. “At 12 months, the placebo group had a 5.1% lower proteinuria level than compared to baseline,” Dr. Perkovic said. “But in the sibiprenlimab group, that proteinuria reduction is now down to 56.6%. for a difference between the two arms of 54.3%. So there's a suggestion that even at 12 months, the effect on proteinuria may still be increasing.”
Subgroup data was also presented for the first time. Across a pre-specified a number of subgroups, the benefits appeared to be consistent. Another observation was that proteinuria effectively returned to almost normal. “We call remission from proteinuria less than half a gram a day, and the proportion in the sibiprenlimab group was 34.3% compared to 12.7% in placebo,” he noted. “We also looked at the changes in the proportion of people who had hematuria. That progressively fell over the course of the study, so that at 12 months, only about 20% of patients in the sibiprenlimab group still had blood in their urine.”
Safety data showed that there was no increase in the risk of adverse events overall, or an increase in the risk of serious adverse events, and there were no deaths reported in the trial.
He noted that the trial is ongoing and that the safety and efficacy outcomes on kidney function will be assessed at 24 months. The FDA has already granted a biologics license application (BLA) for sibeprenlimab, and has given sibeprenlimab a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2025.
“We hope to hear soon about that decision, and the full results of the eGFR data will be available next year,” Dr. Perkovic concluded
The VISIONARY trial is sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.
Relevant disclosures for Dr Perkovic include Boehringer Ingelheim,AbbVie, Inc., Bristol-Myers Squibb, servier, Astellas Pharma US, Merck, Janssen Pharmaceuticals, GSK, and others.
SA-OR086 Sibeprenlimab for the Treatment of IgAN: VISIONARY Phase 3 Interim and Prespecified Subgroup Analyses. Presented at: Kidney Week 2025; November 5-9, 2025; Houston
Illustration by Diana Connolly
