Sibeprenlimab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial
In the phase 3 VISIONARY interim analysis, the APRIL inhibitor sibeprenlimab lowered proteinuria by roughly 51% relative to placebo at 9 months in patients with IgA nephropathy, with a safety profile similar to placebo.
Background
IgA nephropathy is the most common primary glomerulonephritis and a leading cause of kidney failure. The cytokine APRIL (a proliferation-inducing ligand) is considered a key driver of disease, promoting B-cell production of pathogenic galactose-deficient IgA1. Sibeprenlimab is a humanized IgG2 monoclonal antibody that selectively binds and inhibits APRIL.
Study design
VISIONARY was a phase 3, multicenter, double-blind, randomized, placebo-controlled trial that assigned 510 adults with biopsy-confirmed IgA nephropathy 1:1 to subcutaneous sibeprenlimab 400 mg or placebo every 4 weeks for 100 weeks. The primary endpoint of this prespecified interim analysis was change in the 24-hour urinary protein-to-creatinine ratio at 9 months, assessed in the first 320 patients who had the opportunity to complete that evaluation.
Key findings
At 9 months the 24-hour urinary protein-to-creatinine ratio fell by 50.2% with sibeprenlimab versus a 2.1% increase with placebo, corresponding to a 51.2% lower adjusted geometric mean ratio with sibeprenlimab (96.5% CI, 42.9 to 58.2; P<0.001). By week 48, APRIL and galactose-deficient IgA1 were reduced from baseline by 95.8% and 67.1%, respectively. The safety profile appeared similar between groups, with no deaths and serious adverse event rates of 3.5% with sibeprenlimab and 4.4% with placebo.
Clinical implications
Sibeprenlimab produced a clinically meaningful, upstream reduction in proteinuria and pathogenic IgA, supporting APRIL inhibition as a disease-modifying strategy in IgA nephropathy. The key secondary endpoint, the annualized eGFR slope over 24 months, is to be reported at trial completion and will determine the durability of kidney-function benefit.
Category
Research
Source
The New England Journal of Medicine
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