FDA Approves Novartis’ Oral Fabhalta as First Treatment for C3G

The FDA on Thursday approved Fabhalta (iptacopan) to treat complement 3 glomerulopathy (CG3), a progressive, ultrarare kidney disease with a poor prognosis for patients who previously could rely only on supportive care and often faced significant challenges.

Fabhalta, marketed by the Swiss multinational Novartis AG, is the first and only treatment to reduce the buildup of proteinuria (protein in the urine) as a result of inflammation caused by CG3.

“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, M.D., professor of pediatrics-nephrology at the University of Iowa and co-investigator of the pivotal Phase III APPEAR-C3G study, said in a March 20, 2025, news release from Novartis.

The average age of diagnosis with C3G is about 23 years. About half of people living with the disease progress to kidney failure within 10 years, requiring lifelong dialysis and/or kidney transplantation. People living with C3G also may experience high levels of fatigue, mobility issues and mental health symptoms such as depression and anxiety.

“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,” Nester said in the release.

Fabhalta was previously approved in December 2023 for paroxysmal nocturnal hemoglobinuria (PNH) and received accelerated approval in August 2024 for immunoglobulin A nephropathy (IgAN).

The latest approval followed the presentation of 12-month results of the APPEAR-C3G study evaluating the safety and efficacy of twice-daily oral iptacopan in adult patients at the American Society of Nephrology Kidney Week in San Diego in October 2024.

The study consisted of a six-month randomized, double-blind treatment period with Fabhalta compared with placebo plus supportive care, followed by an additional six-month open-label period during which all participants received the therapy.

Treatment with the drug resulted in a clinically meaningful reduction in proteinuria as early as 14 days and sustained at 12 months. Proteinuria reduction was similarly seen in placebo group participants who received active therapy during the open-label period.

The most common adverse reactions during the trial, seen in 10% or fewer participants, were nasopharyngitis and viral infections. Fabhalta affects part of the immune system and may cause serious infections. It must be administered through a Risk Evaluation and Mitigation Strategy (REMS) that requires specific vaccinations. A boxed warning is included in the prescribing information.

C3 glomerulopathy damages the glomeruli in the kidney, according to an explanation of the disease posted on the American Kidney Fund’s website. It comes in two types: dense deposit disease and C3 glomerulonephritis. Both cause similar kidney problems, although some studies suggest that patients with the dense deposit disease have a more severe course.

C3 glomerulopathy affects persons of all ages, although the average age appears to be lower in patients with dense deposit disease compared with those with C3 glomerulonephritis, according to the National Organization for Rare Disorders. The prevalence of C3 glomerulopathy is estimated to be 2 to 3 per 1,000,000 people. Extrapolating that ratio to the U.S. population means that there are between 680 and 1,020 in the United States living with the disease.

Fabhalta has a wholesale acquisition cost of $566,500 per year. Novartis offers a $0 copay program for commercially insured patients that has a limit of $20,000 annually. Based upon the payer mix, the majority of Fabhalta patients will be commercially insured, and the majority of these patients in the United States may pay as little as $0 for their copay, according to a company spokesperson.

The company also offers Novartis Patient Support, a comprehensive program that provides personalized support to assist patients in navigating their insurance coverage and identifying financial assistance options while also offering educational resources to help them get started on treatment and guide them along the way.

Novartis said it is studying Fabhalta in multiple other rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN).