Novartis AG presented results from the 6-month double-blind period of the Phase III APPEAR-C3G study of Fabhalta (iptacopan) at the late-breaking clinical trials session of the European Renal Association (ERA) Congress ). Patients treated with Fabhalta in addition to supportive care achieved a 35.1% (p=0.0014) reduction in proteinuria (measured by 24-hour urine protein-to-creatinine ratio). [UPCR’]) at 6 months, compared to placebo in addition to supportive care1. Fabhalta is an oral alternative complement pathway factor B inhibitor studied in adult patients with C3 glomerulopathy (C3G)1-3. Regulatory submissions, notably to the FDA and EMA, for the C3G indication in adults are planned for the second half of 2024.
The APPEAR-C3 G study continues with an additional 6-month, open-label period after the 6-month double-blind period, during which all patients receive Fabhalta, including those previously receiving placebo. These data will be presented at an upcoming medical meeting when they become available. At ERA, Novartis will also present new data across its entire rare disease portfolio, including results for investigational atrasentan in IgA nephropathy (IgAN), from the 36-week interim analysis of the phase III ALIGN study, as well as additional data on Fabhalta in IgA nephropathy from the 9-month interim analysis of the phase III APPLAUSE-IgAN study, long-term efficacy and safety data 33-month term for Fabhalta in C3G from the phase II extension study, one-year phase I/II data for investigational zigakibart in IgAN, and data from real-world studies in C3G and atypical hemolytic uremic syndrome (aHUS)16-19.
Fabhalta was approved by the FDA in December 2023 and by the EMA in May 2024 for the treatment of adults with a rare blood disorder, paroxysmal nocturnal hemoglobinuria (PNH)21,22. C3G is an ultra-rare progressive kidney disease that initially occurs in children and young adults4-6,23. Each year, approximately 1 to 2 people per million worldwide are newly diagnosed with C3G, a form of membranoproliferative glomerulonephritis (MPGN).
In the case of C3G, hyperactivation of the alternative complement pathway – part of the immune system – causes C3 protein deposits to build up in the kidney glomeruli (a network of blood vessels that filter waste and remove excess blood fluids)4,7,23-25.
This triggers inflammation and glomerular damage that results in proteinuria (protein in the urine), hematuria (blood in the urine), and reduced kidney function4,7,23-25. Approximately 50% of patients with C3G progress to renal failure within 10 years of diagnosis, and must then resort to dialysis and/or kidney transplantation6,7, and more than 55% of patients with C3G experience disease recurrence after transplantation26-29.
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