Novartis' Fabhalta (iptacopan) has demonstrated sustained, clinically meaningful results at one year in patients with C3 glomerulopathy (C3G), according to data presented from the Phase III APPEAR-C3G study at the American Society of Nephrology (ASN) Kidney Week 2024. The data confirm that treatment with Fabhalta resulted in clinically meaningful proteinuria reduction, observed as early as 14 days and sustained at 12 months.
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 included a 6-month randomized, double-blind treatment period comparing Fabhalta to placebo, followed by a 6-month open-label treatment period where all participants received Fabhalta. Results presented earlier at the 2024 European Renal Association (ERA) Congress showed a statistically significant and clinically meaningful 35.1% proteinuria reduction versus placebo at 6 months.
Longer-term data from the APPEAR-C3G study indicate that the proteinuria reduction was sustained over one year. Furthermore, an exploratory analysis showed improvement in estimated glomerular filtration rate (eGFR) slope upon Fabhalta initiation, compared to patients' historical rapid decline. This suggests a potential for Fabhalta to slow the progression of kidney function loss in C3G 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 and APPEAR-C3G Co-Investigator and Steering Committee Member, 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."
Safety Profile and Regulatory Status
Fabhalta demonstrated a favorable safety profile throughout the 12-month study period, with most treatment-emergent adverse events being mild to moderate in severity. There were no deaths, cases of meningitis or meningococcal sepsis, and no discontinuations due to treatment-emergent adverse events.
Regulatory submissions for Fabhalta in C3G are completed in the EU, China, and Japan, with a US submission expected by the end of the year. Fabhalta has received FDA approval for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and accelerated approval for the reduction of proteinuria in certain adults with primary 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.
