Ravulizumab in IgA Nephropathy: Phase 2 Trial Readout

Key Takeaways

• During the randomized period, ravulizumab was associated with a greater reduction in proteinuria than placebo at week 26 (−41.9% vs −16.8%; treatment effect 30.1%; P = 0.005).
• Investigators reported a trend toward eGFR stabilization (least squares mean change at week 26: 0.2 vs −4.5 ml/min per 1.73 m2 for ravulizumab vs placebo) and described adverse-event profiles as similar between groups.
• Adults were randomized 2:1 to intravenous dosing every 8 weeks before an open-label period for all participants, and phase 3 enrollment is ongoing.

The blinded comparison tested ravulizumab versus placebo during the initial treatment period, with standard care continued. At week 26, the prespecified proteinuria outcome showed a statistically significant reduction with ravulizumab versus placebo (−41.9% vs −16.8%; treatment effect 30.1%; P = 0.005). Investigators also reported kidney-function findings, safety observations, and development updates.

Adults with IgA nephropathy entered the trial on stable renin-angiotensin blockade as background therapy. Eligibility also required proteinuria of at least 1 g/day and an eGFR of at least 30 mL/min/1.73 m2. Participants were assigned 2:1 to intravenous ravulizumab every 8 weeks or placebo for 26 weeks; from week 26 through week 50, all participants received open-label ravulizumab.

The primary efficacy measure was percentage change in proteinuria from baseline to week 26. This prespecified endpoint favored ravulizumab during the randomized period, and the week-26 difference was reported as statistically significant. In their Conclusions, investigators described the proteinuria reduction with ravulizumab as early and sustained. Follow-up continued through week 50 after crossover to open-label ravulizumab for all participants, although placebo-controlled comparisons were limited to the blinded period through week 26.

Investigators also observed a trend toward eGFR stabilization during the blinded comparison, with a smaller mean decline in the ravulizumab group than in the placebo group. Kidney-function follow-up extended into the open-label period. Safety findings were presented separately, with adverse events described as similar between groups and ravulizumab characterized as well tolerated; individual adverse events were not detailed in the summary.

The authors framed these phase 2 findings within ongoing development and noted that a phase 3 trial is enrolling (NCT06291376).