FDA Approves Novartis Oral Treatment for Adults with C3 Glomerulopathy

Oral Fabhalta (iptacopan), developed by Novartis, has been approved by FDA for treatment of adults with C3 glomerulopathy (C3G) to reduce proteinuria in those patients, the first approved treatment for that condition (1). C3G is a progressive, ultra-rare kidney disease with an average age at diagnosis of approximately 23 years old; approximately half of those diagnosed progress to kidney failure within 10 years, requiring lifelong dialysis and/or a kidney transplant.

C3G is further described by Novartis as an overactivation of a part of the immune system, the alternative complement pathway, that causes deposits of C3 protein to build up in kidney glomeruli, the blood vessel network that filters waste and removes extra fluid from blood (1). This can result in inflammation and/or glomerular damage causing proteinuria, or protein in urine, hematuria (blood in urine), and reduced function of the kidneys. The disease has previously been typically treated with a combination of supportive care, broad immunosuppression, and symptom management.

FDA has approved Novartis’ oral iptacopan treatment twice before; in December 2023, for treatment of adults with paroxysmal nocturnal hemoglobinuria, and August 2024, for reduction of proteinuria in adults with primary immunoglobulin A nephropathy who are at risk of rapid disease progression (1).

A Phase III trial (APPEAR-C3G), in which iptacopan was taken orally twice daily, showed clinically meaningful proteinuria reduction as early as 14 days, and sustained at 12 months (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,” Carla Nester, MD, professor of Pediatrics-Nephrology at the University of Iowa, and APPEAR-C3G study co-investigator, said in a Novartis press release (1). “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 most common adverse reactions in the Phase III study were nasopharyngitis and viral infections; meanwhile, the symptoms not specifically tied to kidney function that patients with C3G may face include high levels of fatigue, certain mobility issues that can affect day-to-day activities, and mental health effects including depression and anxiety (1).

“As someone whose family has suffered from C3G across multiple generations, it is difficult to fully express the physical and emotional challenges of living with this unrelenting disease,” said Lindsey Fuller, C3G patient and co-leader of C3G Warriors. “To finally have an approved treatment—and one that can be taken orally—is something people with C3G have been waiting for. Today’s approval brings new hope for me, my family, and so many others.”

Prior to FDA’s decision, announced in the March 21, 2025 Novartis press release, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) at its February 24–27 meeting extended the indication for iptacopan to include treatment of adult patients with C3G (2).

“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 company’s 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. Novartis Receives Third FDA Approval for Oral Fabhalta (iptacopan)—The First and Only Treatment Approved in C3 Glomerulopathy (C3G). Press Release. March 21, 2025.
2. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 February 2025. Press Release. Feb. 28, 2025.