Sibeprenlimab is an emerging treatment option for IgA nephropathy

In patients with IgA nephropathy at risk of progression, sibeprenlimab versus placebo has shown a 50% reduction in urinary protein-creatinine ratio (uPCR) after 9 months of treatment, with similar safety, according to the VISIONARY trial.

Prof. Vlado Perkovic (University of New South Wales, Australia) reported interim results from VISIONARY (NCT05248646), an ongoing, phase 3, multicentre, randomised, double-blind trial of sibeprenlimab, an IgG2 antibody targeting the APRIL (A proliferation-inducing ligand) protein [1]. Adult trial participants had biopsy-confirmed IgA nephropathy, uPCR ≥0.75 g/g or uPCR ≥1 g/day, eGFR ≥30 mL/min/1.73 m², and were on a stable dose of ACE inhibitors or angiotensin receptor blocker with/without SGLT2 inhibitors for ≥3 months. A total of 530 participants were randomised 1:1 to subcutaneous sibeprenlimab 400 mg every 4 weeks or placebo, and the primary endpoint was uPCR ratio at 9 months.

The initial analysis presented by Prof. Perkovic included 320 patients. Spot uPCR values tended to decrease over time with sibeprenlimab, and tended to increase with placebo. After 9 months, sibeprenlimab led to a -50.2% change in uPCR, compared with a +2.1% change with placebo (-51.2% placebo-corrected effect; 95% CI -42.9 to -58.2%; P<0.0001). Safety tended to be similar between the treatment arms; adverse events that were more common with sibeprenlimab compared with placebo included upper respiratory tract infection (17.8%), injection-site pain (13.2%), COVID-19 infection (12.5%), nasopharyngitis (11.8%), and influenza (8.6%).

“VISIONARY is the largest phase 3 trial to date in patients with IgA nephropathy,” noted Prof. Perkovic. “Subcutaneous treatment with sibeprenlimab was well-tolerated, with overall reassuring safety data, and in this trial, it reduced uPCR by 51.2% at 9 months, the largest numerical effect reported in all phase 3 trials thus far. The full analysis of the trial is ongoing, and the results are expected next year.”

1. Perkovic V, et al. Sibeprenlimab for patients with IgA nephropathy: Results from a prespecified interim analysis of the phase 3 VISIONARY study. 62nd ERA Congress, 4–7 June 2025, Vienna, Austria.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 10 June 2025