Novartis Fabhalta's Breakthrough for C3G

Novartis has shared positive one-year results for its oral drug Fabhalta® (iptacopan) from the Phase III APPEAR-C3G trial, showing significant clinical benefits for patients with C3 glomerulopathy (C3G), an extremely rare kidney disease with no approved treatments. Presented at the ASN Kidney Week 2024, the data demonstrate that Fabhalta maintained substantial proteinuria reduction over 12 months, with improvements in kidney function as measured by estimated glomerular filtration rate (eGFR) slope—a critical kidney health metric—compared to the patients' previous rapid decline. Additionally, Fabhalta exhibited a favorable safety profile without any new safety concerns.

The APPEAR-C3G study tested Fabhalta’s efficacy and safety in adults with C3G over a 6-month double-blind period against a placebo, followed by a 6-month open-label period where all patients received the drug. Initial findings presented at the 2024 ERA Congress showed Fabhalta achieved a 35.1% proteinuria reduction at six months compared to placebo when added to supportive care. Sustained results over a year underscore Fabhalta’s potential as a much-needed oral treatment specifically targeting C3G’s underlying mechanism via the alternative complement pathway.

Dr. Carla Nester of the University of Iowa and APPEAR-C3G co-investigator emphasized the drug’s potential impact on young C3G patients, who currently face limited treatment options. Dr. Andrew Bomback from Columbia University, another trial co-investigator, highlighted the findings as pivotal in potentially transforming the C3G treatment landscape.

Regulatory applications for Fabhalta in C3G have been submitted in the EU, China, and Japan, with U.S. submission expected by the end of 2024. If approved, Fabhalta would be the first oral alternative complement pathway inhibitor available for C3G patients, half of whom progress to kidney failure within a decade, requiring dialysis or transplantation.

Fabhalta has already received FDA approval for treating paroxysmal nocturnal hemoglobinuria (PNH) in late 2023 and conditional approval for proteinuria reduction in IgA nephropathy (IgAN) earlier in 2024. In addition, Novartis is conducting studies on Fabhalta for other rare kidney diseases, including aHUS, IC-MPGN, and lupus nephritis, as part of its broader commitment to kidney disease treatment innovation.