Interim Analysis of a Phase 3 Trial of Povetacicept in IgA Nephropathy.

In 30 seconds

This prespecified interim analysis of an ongoing, multicenter, phase 3 randomized, double-blind, placebo-controlled trial evaluated povetacicept in participants with biopsy-proven IgA nephropathy receiving stable background therapy. Among the first 199 randomized participants included in efficacy analyses, the 24-hour urinary protein-to-creatinine ratio at week 36 decreased by 52.0% with povetacicept and 4.3% with placebo (adjusted difference, -49.8 percentage points; 95% CI, -58.6 to -39.2; P<0.001). Galactose-deficient IgA1 and hematuria also improved more with povetacicept. Adverse-event incidence was similar between groups.

Key findings

• At week 36, the 24-hour urinary protein-to-creatinine ratio decreased by 52.0% with povetacicept and 4.3% with placebo (adjusted difference, -49.8 percentage points; 95% CI, -58.6 to -39.2; P<0.001).
• Galactose-deficient IgA1 decreased by 77.4% with povetacicept and increased by 9.1% with placebo (adjusted difference, -79.3 percentage points; 95% CI, -82.2 to -75.9; P<0.001).
• Among participants with baseline hematuria, resolution occurred in 85% with povetacicept and 23% with placebo (adjusted difference, 62 percentage points; 95% CI, 45 to 78; P<0.001).
• Adverse events occurred in 75% with povetacicept and 78% with placebo; serious adverse events occurred in 3% and 4%, respectively.

Why it matters

The trial reports substantial short-term reductions in proteinuria, a key measured outcome in IgA nephropathy, alongside changes in disease-related biomarkers and hematuria. These findings provide randomized evidence for dual BAFF and APRIL inhibition in this population. The results are interim and concern outcomes measured at week 36, so they do not establish longer-term kidney outcomes.

What to keep in mind

This is an interim analysis of an ongoing trial; efficacy analyses included the first 199 randomized participants, and outcomes were assessed at week 36.