Novartis presented promising 12-month results from its Phase III APPEAR-C3G study at the 2024 American Society of Nephrology (ASN) Kidney Week. These findings show that patients with C3 glomerulopathy (C3G) who received oral Fabhalta® (iptacopan) alongside supportive care maintained clinically meaningful outcomes for a year.
The study demonstrated a significant reduction in proteinuria, noticeable as early as 14 days and sustained over 12 months. Patients who switched to Fabhalta during the open-label phase also saw proteinuria improvements. Furthermore, patients showed improvement in estimated glomerular filtration rate (eGFR) slope, contrasting with their previous rapid decline. Fabhalta was well-tolerated, with no new safety concerns reported.
APPEAR-C3G evaluated the safety and efficacy of twice-daily Fabhalta in adults with C3G, consisting of an initial 6-month, randomized, double-blind period (Fabhalta vs. placebo), followed by a 6-month open-label period where all participants received Fabhalta. Previous findings presented at the 2024 European Renal Association (ERA) Congress revealed a statistically significant 35.1% reduction in proteinuria compared to placebo at the 6-month mark.
Dr. Carla Nester, Co-Investigator and Professor of Pediatrics-Nephrology at the University of Iowa, remarked on the urgent need for dedicated C3G treatments, noting that Fabhalta could provide new hope as the first oral complement inhibitor specifically for C3G.
Dr. Andrew Bomback, Co-Investigator and Associate Professor at Columbia University, added that these results represent a milestone in managing C3G, offering the first longer-term data on treatments targeting the disease’s underlying mechanisms via the alternative complement pathway.
About half of C3G patients progress to kidney failure within a decade of diagnosis, requiring dialysis or kidney transplantation. Fabhalta, the only oral Factor B inhibitor targeting the alternative complement pathway, could become the first FDA-approved treatment for C3G. Regulatory submissions are complete in the EU, China, and Japan, with a U.S. submission expected by year-end.
David Soergel, M.D., Global Head of Cardiovascular, Renal, and Metabolism Development at Novartis, expressed enthusiasm about Fabhalta’s potential and Novartis’ commitment to regulatory collaboration to bring this treatment to C3G patients. Building on its nephrology experience and a recent IgA nephropathy approval, Novartis aims to transform care with its broad kidney disease portfolio.
Fabhalta, initially FDA-approved in 2023 for paroxysmal nocturnal hemoglobinuria (PNH) and recently for reducing proteinuria in primary IgA nephropathy, is also under study for other rare kidney diseases. In addition, Novartis is progressing two further IgAN treatments: atrasentan, an oral endothelin A receptor antagonist, and zigakibart, a monoclonal antibody currently in Phase III.
