Iptacopan Preserves Kidney Function in IgA Nephropathy: NEJM | August 2026

Introduction:

IgA nephropathy is a progressive immune-mediated kidney disease in which alternative complement pathway activation contributes to glomerular inflammation and renal injury. Iptacopan is an oral selective complement factor B inhibitor that targets this pathway. The APPLAUSE-IgAN phase 3 trial evaluated whether its previously demonstrated reduction in proteinuria translates into sustained preservation of kidney function over 24 months.

Why was this study needed?

. Persistent proteinuria in IgA nephropathy is associated with progressive loss of kidney function despite optimized supportive care.

. Alternative complement pathway activation is an important disease mechanism and represents a targeted therapeutic opportunity.

. Earlier APPLAUSE-IgAN results demonstrated substantial proteinuria reduction with iptacopan, but long-term renal benefit required confirmation.

. Preservation of eGFR and prevention of kidney failure are clinically more meaningful outcomes than proteinuria reduction alone.

Results:

Among 477 patients, iptacopan significantly slowed deterioration in kidney function over 24 months. The annualized eGFR decline was −3.10 mL/min/1.73 m²/year with iptacopan versus −6.12 with placebo, representing approximately a halving of the rate of kidney function loss. The composite kidney-failure outcome occurred in 21.4% versus 33.5%, corresponding to a 43% lower relative risk with iptacopan. Overall adverse-event and serious adverse-event rates were similar between groups. However, serious infections occurred more frequently with iptacopan, an important consideration with complement inhibition. No deaths occurred during the study.

Clinical Impact:

These final data establish that targeted inhibition of the alternative complement pathway provides benefits extending beyond proteinuria reduction to clinically meaningful preservation of renal function. Iptacopan therefore represents a mechanism-based disease-modifying strategy for patients with IgA nephropathy who remain at risk of progression despite supportive therapy.

Bottom Line:

Iptacopan significantly slowed eGFR decline and reduced kidney-failure events over 24 months in IgA nephropathy, providing strong evidence that alternative complement pathway inhibition can modify long-term disease progression.