Iptacopan Slows Kidney Function Decline in IgA Nephropathy, Phase III Trial Confirms

A phase III clinical trial has demonstrated that iptacopan, an oral selective inhibitor of the alternative complement pathway via Factor B, significantly slowed kidney‑function decline in adults with IgA nephropathy (IgAN), a chronic autoimmune glomerular disease that may lead to kidney failure. These findings add to the growing body of evidence supporting complement‑targeted therapies for a condition long underserved by current treatment options.

The APPLAUSE‑IgAN trial followed about 477 adults with primary IgAN over a two‑year period, evaluating the impact of iptacopan versus placebo on the progression of kidney disease. All participants received background supportive care, including maximally tolerated renin‑angiotensin system (RAS) inhibitors, with or without stable sodium‑glucose cotransporter‑2 (SGLT2) inhibitor therapy. Patients treated with iptacopan experienced a statistically significant and clinically meaningful improvement in the annualized decline of estimated glomerular filtration rate (eGFR), the trial’s primary endpoint for long‑term efficacy.

The trial’s two co‑primary endpoints were a reduction in proteinuria at nine months and change in the eGFR slope over 24 months. Secondary outcomes included the proportion of patients achieving meaningful proteinuria reduction without requiring corticosteroids or other immunosuppressive therapies, time to a composite kidney‑failure event (≥30% decline in eGFR, eGFR <15 mL/min/1.73 m², dialysis, transplant or kidney‑failure death) and changes in fatigue levels. A smaller observational cohort included individuals with more advanced disease (eGFR 20‑30 mL/min/1.73 m²), although this cohort did not contribute to the main efficacy analysis.

Iptacopan was well tolerated throughout the study, with a safety profile consistent with earlier trials. Full results (including detailed eGFR slope data, confidence intervals and subgroup analyses) are expected to be presented at upcoming medical conferences, and the data will be used to support a full (traditional) regulatory submission for IgAN in 2026, following the earlier accelerated approval (2024) for proteinuria reduction.

Originally developed for complement‑mediated disorders (including paroxysmal nocturnal haemoglobinuria and C3 glomerulopathy), iptacopan’s mechanism — blocking Factor B of the alternative complement pathway — targets a contributing driver of glomerular inflammation in IgAN and related conditions.

The results from APPLAUSE‑IgAN reinforce the role of complement activation in the pathogenesis of IgAN and underscore the potential of iptacopan to modify disease trajectory.