Atacicept Reduced Proteinuria in Phase 3 IgA Nephropathy Trial

Key Takeaways

• At week 36, proteinuria declined more with atacicept than with placebo in the prespecified interim phase 3 readout.
• ORIGIN 3 is an ongoing randomized, double-blind, placebo-controlled phase 3 trial with 1:1 assignment and weekly subcutaneous home dosing.
• Adverse events were more frequent with atacicept than placebo, and most were mild or moderate.

In patients with IgA nephropathy, atacicept reduced proteinuria by nearly 46% at week 36, while placebo was associated with a much smaller decline in a prespecified interim phase 3 analysis. Because the comparison came from an interim readout, the findings reflect an ongoing study rather than a completed trial. Proteinuria change at week 36 was the primary endpoint. The report also described randomized allocation, weekly home administration, and overall adverse events in both groups.

The ongoing multicenter, double-blind, randomized, placebo-controlled phase 3 trial included patients with IgA nephropathy and was identified as ORIGIN 3. Participants were assigned in a 1:1 ratio to atacicept 150 mg once weekly, given by subcutaneous self-administration at home, or matching placebo. The prespecified primary endpoint was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. That measure was the main efficacy outcome in the interim report.

The prespecified interim analysis included 203 patients, with 106 assigned to atacicept and 97 assigned to placebo. By week 36, proteinuria had fallen 45.7% from baseline with atacicept and 6.8% from baseline with placebo. The geometric mean between-group difference was 41.8 percentage points in favor of atacicept on the primary endpoint. The 95% confidence interval ranged from 28.9 to 52.3, and the reported P value was less than 0.001. At the reported time point, proteinuria reduction was greater with atacicept than with placebo.

Adverse events occurred in 59.3% of patients receiving atacicept and 50.0% of those receiving placebo in the interim analysis. Most events were mild or moderate in severity.