A NOVEL therapeutic approach targeting the cytokine A Proliferation-Inducing Ligand (APRIL) may significantly reduce proteinuria and disease activity in patients with IgA nephropathy, according to interim findings from the Phase III VISIONARY trial presented at UK Kidney Week 2026.
The investigational monoclonal antibody sibeprenlimab was evaluated in a multicentre, double-blind, placebo-controlled study involving adults with biopsy-confirmed IgA nephropathy who were receiving maximally tolerated supportive therapy. In the prespecified interim analysis of 320 participants, patients were randomised to receive subcutaneous sibeprenlimab 400 mg or placebo every four weeks for up to 100 weeks.
Significant Reduction in Proteinuria at 12 Months
At 12 months, treatment with sibeprenlimab resulted in a 56.6% reduction in 24-hour urine protein creatinine ratio (uPCR-24h), compared with a 5.1% reduction in the placebo group. The therapy also demonstrated early and sustained improvements in spot uPCR, with reductions observed from Week 4 and maintained through 12 months.
Rates of proteinuric remission were notably higher in the sibeprenlimab group, with 34.3% of patients achieving remission at 12 months compared with 12.7% of those receiving placebo. Improvements in proteinuria were observed across a range of prespecified patient subgroups, including individuals with both higher and lower baseline proteinuria levels.
The therapy was also associated with reductions in key disease biomarkers. Levels of galactose-deficient IgA1 and APRIL were markedly reduced in patients treated with sibeprenlimab by Week 48. In addition, the proportion of patients with haematuria declined substantially. Among those who were haematuria-positive at baseline, only 19.8% of patients receiving sibeprenlimab remained dipstick-positive at Week 48, compared with 69.0% of patients in the placebo group. Kaplan-Meier analyses indicated that patients receiving sibeprenlimab were more likely to achieve haematuria-negative status earlier, with a median time to negativity of 25 weeks.
Safety outcomes were comparable between the treatment and placebo groups, and no deaths were reported during the interim analysis period.
Long-Term Outcomes to Be Assessed
Taken together, the findings suggest that sibeprenlimab may provide disease-modifying benefits for patients with IgA nephropathy by reducing proteinuria and improving key biomarkers associated with disease activity. Longer-term outcomes, including effects on kidney function measured by estimated glomerular filtration rate, will be evaluated at 24 months as the VISIONARY trial continues.
Reference
Barratt J et al. Sibeprenlimab for the treatment of IgA nephropathy: VISIONARY phase 3 interim and prespecified subgroup analyses. UK Kidney Week, 10-12 March, 2026.
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