Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy

IgA nephropathy is the most prevalent type of glomerulonephritis, leading to progressive kidney damage due to immune complex deposition. The alternative complement pathway plays a central role in disease pathogenesis, making complement inhibitors a promising therapeutic avenue. Iptacopan is a first-in-class oral inhibitor that specifically targets factor B, preventing activation of C3 and downstream inflammatory responses.

In this phase 3, randomized, placebo-controlled trial, 443 patients with biopsy-confirmed IgA nephropathy and proteinuria received iptacopan (200 mg) or placebo twice daily for 24 months alongside optimized supportive therapy. An interim analysis at month 9 showed that iptacopan reduced proteinuria by 38.3% (95% CI, 26.0–48.6; P<0.001) compared to placebo, with consistent findings across secondary endpoints. No unexpected safety concerns were observed, and most adverse events were mild to moderate.

IgA nephropathy is the most prevalent type of glomerulonephritis, leading to progressive kidney damage due to immune complex deposition. The alternative complement pathway plays a central role in disease pathogenesis, making complement inhibitors a promising therapeutic avenue. Iptacopan is a first-in-class oral inhibitor that specifically targets factor B, preventing activation of C3 and downstream inflammatory responses.

In this phase 3, randomized, placebo-controlled trial, 443 patients with biopsy-confirmed IgA nephropathy and proteinuria received iptacopan (200 mg) or placebo twice daily for 24 months alongside optimized supportive therapy. An interim analysis at month 9 showed that iptacopan reduced proteinuria by 38.3% (95% CI, 26.0–48.6; P<0.001) compared to placebo, with consistent findings across secondary endpoints. No unexpected safety concerns were observed, and most adverse events were mild to moderate.