FDA Approves Novartis’ Fabhalta for C3 Glomerulopathy

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The FDA has approved Novartis’ Fabhalta (iptacopan) as the first and only treatment for C3 glomerulopathy (C3G). Previously, patients with C3G were forced to rely on supportive care and broad immunosuppression. The regulatory action was based on results from the pivotal Phase III APPEAR-C3G trial, which demonstrated clinically meaningful and sustained proteinuria reduction among patients with C3G administered Fabhalta.¹

“C3G is a debilitating disease often affecting young people, impacting many aspects of their physical and emotional health, and our previous treatment options came with significant challenges,” APPEAR-C3G study co-investigator Carla Nester, MD, MSA, FASN, professor of pediatrics-nephrology, University of Iowa, said in a press release. “This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients.”

The multicenter, randomized, double-blind, parallel-group, placebo-controlled APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in 74 patients with native kidney C3G. During the six-month double-blind period, patients were randomly assigned in a 1:1 ratio to receive either Fabhalta or placebo in addition to supportive care. After this period, all patients received Fabhalta for an additional six months. The primary endpoint was reduction of proteinuria from baseline after six months in the double-blind period.^1,2

At the six-month mark, the study showed that Fabhalta reduced protein levels in the urine by 35.1% compared to the placebo group, with effects lasting up to one year. Additionally, 43.5% of patients in the Fabhalta group showed kidney health improvement compared to 25% of those who switched from placebo. The treatment also appeared to slow kidney function decline compared to historical trends in C3G patients.²

The most common adverse events associated with Fabhalta were nasopharyngitis and viral infections. Overall, the treatment demonstrated a favorable safety profile, with no new safety signals identified.

The latest approval for Fabhalta is its third overall and its second indication approved in kidney disease since August 2024. Fabhalta was first approved in December 2023 for adults with paroxysmal nocturnal hemoglobinuria. It was also granted accelerated approval to reduce proteinuria in adults with primary immunoglobulin A nephropathy who are at risk of rapid disease progression, with continued approval dependent on confirmatory evidence. Additionally, Fabhalta is also being investigated as a potential treatment for several other kidney diseases, including atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis.¹

C3G is a rare and serious kidney disease that can affect patients of all ages, with an estimated prevalence of 2 to 3 cases per million people.³ A Cleveland Clinic study estimates 0.5 to 3 new cases per million people annually in the United States, with a total prevalence of 14 to 40 cases per million at any given time. Approximately 50% of patients with C3G progress to end-stage kidney disease within 10 years of diagnosis.⁴

“We extend our deepest gratitude to the patients and investigators who participated in our clinical trials, without whom this first FDA approval in C3G wouldn’t have been possible,” said Victor Bultó, president, US, Novartis, in the press release. “With this additional approval for Fabhalta—the second in kidney disease—we will leverage our established capabilities and expertise to bring this innovative treatment to patients in need as we work to help transform care for people living with kidney diseases.”

References

1. Novartis receives third FDA approval for oral Fabhalta® (iptacopan) – the first and only treatment approved in C3 glomerulopathy (C3G). Novartis. March 21, 2025. Accessed March 21, 2025. https://www.novartis.com/news/media-releases/novartis-receives-third-fda-approval-oral-fabhalta-iptacopan-first-and-only-treatment-approved-c3-glomerulopathy-c3g

2. WCN25-2041 EFFICACY AND SAFETY OF IPTACOPAN IN PATIENTS WITH C3 GLOMERULOPATHY: 12-MONTH RESULTS FROM THE PHASE 3 APPEAR-C3G STUDY. ScienceDirect. Accessed March 21, 2025. https://www.sciencedirect.com/science/article/pii/S2468024924023222

3. C3 Glomerulopathy: Dense Deposit Disease and C3 Glomerulonephritis. NORD. Accessed March 21, 2025. https://rarediseases.org/rare-diseases/c3-glomerulopathy-dense-deposit-disease-and-c3-glomerulonephritis/#disease-overview-main

4. C3 glomerulopathy. Ali Mehdi, MD, MEd, FACP, FASN and Jonathan J. Taliercio, DO, FASN Cleveland Clinic Journal of Medicine June 2023, 90 (6 suppl 1) e1-e4; DOI: https://doi.org/10.3949/ccjm.90.e-s1.01