Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy

Article Number: SIS591478AI220525

22nd May, 2025

Author(s):

Vlado Perkovic, M.B., B.S., Ph.D.; Jonathan Barratt, Ph.D.; Brad Rovin, M.D.; Naoki Kashihara, M.D., Ph.D.; Bart Maes, M.D., Ph.D.; Hong Zhang, M.D., Ph.D. et al., for the APPLAUSE-IgAN Investigators

Abstract:

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.

Keywords:

IgA nephropathy iptacopan alternative complement pathway factor B inhibition glomerulonephritis proteinuria reduction renal pathology clinical trial complement inhibitors kidney disease therapy