VIENNA — Sibeprenlimab, a novel selective immune antibody, reduced the urine protein-to-creatinine ratio (uPCR) by more than half in patients with immunoglobulin A (IgA) nephropathy, according to an interim analysis of the VISIONARY trial.
Beyond this clinical effect, a notable observation was the lack of safety concerns, especially given that, although sibeprenlimab is a selective agent, there may have been unexpected off-target effects.
“Safety’s been a key consideration with these drugs,” study presenter Vlado Perkovic, MD, PhD, provost and scientia professor, University of New South Wales, Sydney, Australia, told Medscape Medical News.
Sibeprenlimab represents a new mechanism of action and “we don’t yet fully understand the profile, so we’ve been looking at that data very carefully,” explained Perkovic. “In particular, the infection risk has been my biggest concern, given we know that infections are dramatically increased in people with steroid therapy for example, in IgA nephropathy.”
The results of the trial — the largest to date in the field — were presented at the 62nd European Renal Association Congress 2025 on June 6 and drew a warm applause from the audience.
An Underestimated Condition
IgA nephropathy is estimated to affect 2.5 per 100,000 people per year, although “it’s possible that that number is a significant underestimate,” said Perkovic.
Diagnosis typically occurs between 20 and 40 years of age. And, despite supportive care, the majority of patients have a high lifetime risk of end-stage kidney disease (ESKD), with up to 50% of patients progressing to ESKD within 20 years of their clinical presentation.
“It’s quite likely we’ve underestimated just how important this condition is,” said Perkovic, but “we’re fortunate that we’re in the middle of something of a golden age of developing new treatments.”
A number of therapies have been shown to reduce the risks associated with the disease, although they do not necessarily address the immunological basis of the condition.
In addition to newer treatments, “corticosteroids have long been used for people with IgA nephropathy,” Perkovic said, “but of course, corticosteroids also have a range of different effects across the immune system,” which can lead to adverse outcomes.
Sibeprenlimab is a selective IgG2 antibody that binds to and inhibits the biological activity of APRIL (a proliferation-inducing ligand), which is produced by mucosal epithel