A recent study has indicated that sibeprenlimab, a novel selective immune antibody, has shown promise in treating immunoglobulin A (IgA) nephropathy. The interim analysis of the VISIONARY trial demonstrated that the drug reduced the urine protein-to-creatinine ratio (uPCR) by more than 50% in patients.

According to Vlado Perkovic, MD, PhD, provost and scientia professor at the University of New South Wales, Sydney, Australia, “Safety’s been a key consideration with these drugs.” He added that while sibeprenlimab is a selective agent, researchers have been vigilant about potential off-target effects, especially concerning infection risks.

the results of the trial, which were presented at the 62nd European Renal Association Congress 2025 on June 6, were well-received.

IgA Nephropathy: An Overlooked Condition

iga nephropathy,a kidney disease,is thought to affect approximately 2.5 in 100,000 people annually,though Vlado Perkovic suggests this figure might be an underestimate. The condition is usually diagnosed in individuals between 20 and 40 years old. A significant number of patients face a high lifetime risk of end-stage kidney disease (ESKD), with about half progressing to ESKD within 20 years of diagnosis.

“It’s quite likely we’ve underestimated just how important this condition is,”

While several therapies can alleviate the risks linked to the disease, they may not target its underlying immunological causes. Corticosteroids,for instance,have been a long-standing treatment option,but their broad effects on the immune system can lead to unwanted outcomes,according to Perkovic.

Sibeprenlimab functions by binding to and inhibiting APRIL (a proliferation-inducing ligand),a protein that affects B cells and plays a role in IgA nephropathy’s development. By targeting APRIL, sibeprenlimab aims to disrupt the 4-Hit process that leads to kidney damage.

VISIONARY Trial: A Phase 3 Study

Following the phase 2 ENVISION trial, researchers initiated the phase 3 VISIONARY trial. This ongoing study involves IgA nephropathy patients from 240 sites across 31 countries. Participants were randomly assigned to receive either sibeprenlimab or a placebo for 100 weeks, followed by a 12-week observation period.

Patients enrolled in the trial had a uPCR of ≥ 0.75 g/g or urine protein excretion of ≥ 1.0 g/day, and an estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m². They were also required to be on a stable dose of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, with or without a SGLT2 inhibitor, for at least 3 months before the study began.

The interim analysis included 320 randomized patients (152 in the sibeprenlimab group and 168 in the placebo group). The primary focus was the change in 24-hour uPCR at 9 months compared to baseline. Further data on eGFR and other outcomes are expected in 2026.

the patients’ median age was 42-43 years. The sibeprenlimab group had fewer females (34.2%) compared to the placebo group (40.5%). Most patients were Asian,with 61.8% in the sibeprenlimab group and 56.5% in the placebo group.

Sibeprenlimab led to a 50.2% reduction in uPCR, while the placebo group saw an increase. This resulted in a significant placebo-adjusted treatment effect of 51.2% (P < .0001). The reduction in uPCR was observed as early as 4 weeks after treatment initiation and continued throughout the follow-up period.

Ronald T. Gansevoort, MD, PhD, a professor of medicine and nephrologist at the University Medical Center Groningen, Netherlands, described the results as “very promising.” He noted that the improvements in proteinuria seen in the VISIONARY trial are the most significant observed to date, but awaits the kidney function results.

Safety Profile

The proportion of patients experiencing treatment-related adverse events was slightly lower with sibeprenlimab (32.9%) compared to placebo (31.0%). Fewer patients on sibeprenlimab discontinued treatment due to adverse events (0.7% vs 2.4%), and there were fewer severe and serious adverse events with the experimental drug.

While infection rates were slightly higher in the sibeprenlimab group, Vlado Perkovic noted that this pattern differed from the phase 2 trials and might be due to chance.He stated that the data so far are encouraging, with no indication of increased infection risk, opportunistic infections, or deaths.

Further data from the ongoing follow-up are needed to confirm these findings. If the final results support the efficacy and safety outcomes observed so far, sibeprenlimab could represent a targeted approach to treating IgA nephropathy.