Novartis has announced positive results from the Phase 3 APPEAR-C3G study, revealing that Fabhalta (iptacopan) demonstrated sustained and clinically meaningful benefits in patients with C3 glomerulopathy (C3G). The study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult C3G patients.
The APPEAR-C3G trial featured a six-month, randomized, double-blind phase comparing Fabhalta to placebo, followed by a six-month open-label phase where all participants received Fabhalta. The data indicated that Fabhalta, when used with supportive care, provided clinically meaningful and sustained results for C3G patients over a 12-month period.
Key Findings from APPEAR-C3G
Treatment with iptacopan led to a clinically meaningful reduction in proteinuria, observed as early as 14 days and sustained at 12 months. Participants who switched to Fabhalta in the open-label phase also experienced a reduction in proteinuria. The study reported a statistically significant and clinically meaningful 35.1% reduction in proteinuria compared to placebo at six months.
Furthermore, the trial observed an improvement in the estimated glomerular filtration rate (eGFR) slope after initiating Fabhalta, contrasting with the historic rapid decline typically seen in C3G patients. Iptacopan also exhibited a favorable safety profile, with no new safety signals identified.
Expert Commentary
David Soergel, Cardiovascular Global Head of the Renal and Metabolism Development Unit at Novartis, 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."
He further added, "Building on the longstanding experience of Novartis in nephrology and our first rare kidney disease approval in IgA nephropathy earlier this year, these results in C3G show continued advancement of our broad, industry-leading portfolio, which aims to transform care for these patients."
Regulatory Landscape and Future Directions
Regulatory submissions for Fabhalta in C3G have been completed in the European Union (EU), China, and Japan, with a submission in the US anticipated by the end of the year. Fabhalta received US Food and Drug Administration (FDA) approval in December 2023 for treating adults with paroxysmal nocturnal haemoglobinuria (PNH). It also secured accelerated approval in August 2024 for reducing proteinuria in specific adults with primary IgA nephropathy (IgAN).
Iptacopan is currently under investigation for various rare kidney diseases, including C3G, atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN). Novartis is also advancing two other IgAN therapies, atrasentan and zigakibart, to expand its portfolio in renal disease treatment.
