Novartis announced positive 12-month data from the Phase III APPEAR-C3G study, revealing that Fabhalta (iptacopan) provided clinically meaningful and sustained benefits for patients with C3 glomerulopathy (C3G). The findings, presented at the American Society of Nephrology (ASN) Kidney Week 2024, highlight Fabhalta's potential as a targeted treatment for this ultra-rare kidney disease.
Sustained Proteinuria Reduction and Improved Kidney Function
The APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study design included a 6-month randomized, double-blind period comparing Fabhalta to placebo, followed by a 6-month open-label extension where all participants received Fabhalta. The results showed that treatment with Fabhalta led to a clinically meaningful reduction in proteinuria, observed as early as 14 days and sustained over 12 months. Furthermore, patients who switched to Fabhalta during the open-label period also experienced proteinuria reduction.
An exploratory analysis revealed an improvement in the estimated glomerular filtration rate (eGFR) slope upon Fabhalta initiation, compared to the patients' historical rapid decline. This suggests a potential for Fabhalta to slow the progression of kidney damage in C3G patients. The safety profile of Fabhalta remained favorable, with no new safety signals identified during the study.
Expert Commentary on Clinical Impact
Carla Nester, Professor of Pediatrics-Nephrology at the University of Iowa and APPEAR-C3G Co-Investigator, emphasized the challenges in treating C3G and the need for dedicated therapies. "I am encouraged to see these data, which reinforce the clinically meaningful impact on kidney health measures we saw at 6 months," she stated. "As the only oral complement inhibitor intended to treat C3G, Fabhalta could provide new hope for people living with this condition."
Andrew Bomback, Associate Professor of Medicine at Columbia University Irving Medical Center and APPEAR-C3G Co-Investigator, 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."
Addressing an Unmet Need in C3G
C3G is a rare and severe kidney disease that often leads to kidney failure, with approximately 50% of patients progressing to end-stage renal disease within 10 years of diagnosis. Currently, there are no approved therapies specifically for C3G, highlighting the significant unmet medical need.
Fabhalta, an oral Factor B inhibitor targeting the alternative complement pathway, has the potential to be the first FDA-approved treatment for C3G. Regulatory submissions for Fabhalta in C3G have been completed in the EU, China, and Japan, with submissions expected in the US by the end of the year.
David Soergel, Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis, expressed enthusiasm about the data and the potential of Fabhalta in C3G. He stated, "We are thrilled to share these data, which demonstrate the potential of Fabhalta in C3G, and look forward to working with regulatory authorities with the goal of bringing this innovative medicine to this patient community."
