Ravulizumab reduced urinary biomarkers in phase 2 IgA nephropathy analysis

Researchers analyzed urine samples from 60 participants with IgA nephropathy in the phase 2 SANCTUARY trial (NCT04564339) and 25 healthy donors. Samples were assessed for markers of complement activation (sC5b-9 and factor Ba), renal inflammation (CD163) and tubular injury (KIM-1 and NGAL). Biomarker levels were normalized to creatinine, and treatment groups were compared over time. The analysis also examined results by baseline proteinuria and estimated glomerular filtration rate (eGFR).

At baseline, sC5b-9, factor Ba, CD163 and KIM-1 levels were higher in participants with IgA nephropathy than in healthy donors (P<0.001); 93% had elevated sC5b-9. Compared with placebo, ravulizumab produced greater reductions in sC5b-9 and factor Ba at weeks 2, 10, 18 and 26, and in CD163 and KIM-1 at weeks 10, 18 and 26 (P<0.05 for all). Reductions were reported through week 50, including after placebo participants crossed over to ravulizumab at week 26.

The findings suggest changes in urinary biomarkers alongside ravulizumab treatment, but this was an exploratory analysis of a small phase 2 trial. The source provides no effect sizes for the biomarker changes, and these results alone do not establish that biomarker reductions translate into improved long-term kidney outcomes or support a change in clinical practice.