FDA Expands Approved Uses of Fabhalta to Include Ultra-Rare Kidney Disease

Rare Daily Staff

The U.S. Food and Drug Administration expanded the approved use of Novartis’ Fabhalta for the treatment of adults with the ultra-rare kidney disease C3 glomerulopathy to reduce protein in the urine, making it the first and only treatment approved for this condition.

C3 glomerulopathy (C3G) is a progressive condition that has been without approved treatments. The average age of diagnosis is around 23 years old. Approximately half of people living with C3G progress to kidney failure within 10 years of diagnosis, requiring lifelong dialysis and/or kidney transplantation. People living with C3G may experience high levels of fatigue, mobility issues affecting everyday life activities, and mental health symptoms, including depression and anxiety.

Fabhalta is a factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell destruction within and outside the blood vessels. It is the only oral inhibitor of the alternative complement pathway to selectively target what is thought to be the underlying cause of C3G. Before the approval of Fabhalta, patients had to rely on supportive care, broad immunosuppression, and symptom management.

The expanded FDA approval follows the FDA’s December 2023 approval of Fabhalta in paroxysmal nocturnal hemoglobinuria (PNH) and its August 2024 accelerated approval in immunoglobulin A nephropathy (IgAN). In February, Fabhalta received a positive CHMP Opinion in C3G by the European Medicines Agency. Regulatory reviews for this indication are ongoing in China and Japan.

The pivotal phase 3 APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study consisted of a six-month, randomized, double-blind treatment period with Fabhalta compared to placebo in addition to supportive care, followed by an additional six-month, open-label treatment period where all participants received Fabhalta.

Treatment with Fabhalta resulted in clinically meaningful proteinuria reduction, which was seen as early as 14 days and sustained at 12 months. Similarly, in the open-label period, proteinuria reduction was seen in participants who switched to Fabhalta.

Fabhalta demonstrated a favorable safety profile, with no new safety signals. In patients with C3G, the most common adverse reactions with Fabhalta were nasopharyngitis and viral infections.

“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,” said Carla Nester, professor of pediatrics-nephrology at the University of Iowa and Fabhalta APPEAR-C3G Study co-investigator. “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.”