Novartis announced positive 12-month data from the Phase III APPEAR-C3G study, revealing that Fabhalta (iptacopan) provided sustained, clinically meaningful results for patients with C3 glomerulopathy (C3G). The findings, presented at the American Society of Nephrology (ASN) Kidney Week 2024, highlight Fabhalta's potential as the first oral treatment targeting the underlying cause of C3G.
Sustained Proteinuria Reduction and Improved Kidney Function
The APPEAR-C3G trial evaluated Fabhalta's efficacy and safety in adult C3G patients. The study included a 6-month randomized, double-blind, placebo-controlled period followed by a 6-month open-label extension where all participants received Fabhalta. Results showed that Fabhalta led to a clinically meaningful reduction in proteinuria, observed as early as 14 days and sustained at 12 months. An exploratory analysis also indicated an improvement in estimated glomerular filtration rate (eGFR) slope upon Fabhalta initiation, compared to the historical rapid decline in these patients.
Expert Commentary
"As a clinician treating young people living with C3G, I see firsthand the challenges with therapies used to treat this condition today, underscoring the vital need for dedicated treatment for these patients," said Carla Nester, M.D., M.S.A., F.A.S.N., Professor of Pediatrics-Nephrology at the University of Iowa and APPEAR-C3G Co-Investigator. "I am encouraged to see these data, which reinforce the clinically meaningful impact on kidney health measures we saw at 6 months... Fabhalta could provide new hope for people living with this condition."
Andrew Bomback, M.D., M.P.H., Associate Professor of Medicine at Columbia University Irving Medical Center, added, "These results mark an important milestone for the management of C3G, as the first study to shed light on longer-term treatment targeting the underlying mechanism of this disease via the alternative complement pathway... I am optimistic that these iptacopan APPEAR-C3G findings bring us a step closer to revolutionizing the treatment paradigm in this ultra-rare disease with no approved therapies."
Fabhalta's Mechanism and Regulatory Status
Fabhalta is an oral Factor B inhibitor of the alternative complement pathway. Regulatory submissions for Fabhalta in C3G are completed in the EU, China, and Japan, with a US submission expected by year-end. It received FDA approval in December 2023 for paroxysmal nocturnal hemoglobinuria (PNH) and accelerated approval in August 2024 for IgA nephropathy (IgAN).
About C3 Glomerulopathy
C3G is an ultra-rare, progressive kidney disease characterized by overactivation of the alternative complement pathway, leading to C3 protein deposits in kidney glomeruli. This results in inflammation, glomerular damage, proteinuria, hematuria, and reduced kidney function. Approximately 50% of C3G patients progress to kidney failure within 10 years of diagnosis.
