Fabhalta (iptacopan) meets Phase III primary endpoint, slows kidney function decline in patients with IgA nephropathy – Novartis

Novartis announced positive final results from APPLAUSE-IgAN, a Phase III study evaluating Fabhalta (iptacopan) in adults living with IgA nephropathy (IgAN). Fabhalta, an oral alternative complement pathway inhibitor, demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years.   In APPLAUSE-IgAN, Fabhalta was well tolerated with a favorable safety profile in line with previously reported data. Full data from the APPLAUSE-IgAN final analysis will be presented at future medical meetings.

Novartis intends to use these data to support Fabhalta submissions in 2026. Alongside Fabhalta, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Vanrafia (atrasentan) and investigational compound zigakibart.

APPLAUSE-IgAN (NCT04578834) is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in 477 adult primary IgAN patients (main study population). Patients were randomized to Fabhalta or placebo, on top of supportive care (a stable dose of maximally-tolerated renin-angiotensin system (RAS) inhibitor therapy with or without a stable dose of SGLT2i).

The two primary endpoints of the study for the interim and final analysis, respectively, are proteinuria reduction at 9 months as measured by UPCR, and the annualized total eGFR slope over 24 months. During the final analysis, the following secondary endpoints were assessed: proportion of participants reaching UPCR <1 g/g without receiving corticosteroids/immunosuppressants or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating kidney replacement therapy (KRT), time from randomization to first occurrence of composite kidney failure endpoint event (reaching either sustained ≥30% decline in eGFR relative to baseline or sustained eGFR <15 mL/min/1.73 m² or maintenance dialysis or receipt of kidney transplant or death from kidney failure), and change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire.

The main study population enrolled patients with an eGFR ≥30 mL/min/1.73 m² and UPCR ≥1 g/g at baseline. In addition, a smaller cohort of patients with severe renal impairment (eGFR 20–30 mL/min/1.73 m² at baseline) was also enrolled to provide additional information but not contributing to the main efficacy analyses.