Novartis oral Fabhalta secures USFDA okay for adults with C3 glomerulopathy

“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, M.D., M.S.A., F.A.S.N., 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.”

Fabhalta is an oral inhibitor of the alternative complement pathway to selectively target what is thought to be the underlying cause of the disease. Before the approval of Fabhalta, patients had to rely on supportive care, broad immunosuppression, and symptom management.

“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.”

C3G is a progressive and ultra-rare kidney disease that, until now, has had no approved treatments. The average age of diagnosis is around 23 years old. Prognosis is poor, with approximately half of people living with C3G progressing 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.

The pivotal Phase III APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study was comprised of a 6-month randomized, double-blind treatment period with Fabhalta compared to placebo in addition to supportive care, followed by an additional 6-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 (≥10%) with Fabhalta were nasopharyngitis and viral infections. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires specific vaccinations.

Last month, Fabhalta received a positive CHMP Opinion in C3G by the European Medicines Agency (EMA). Regulatory reviews for this indication are ongoing in China and Japan.

“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. “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.”

This is the third US approval for Fabhalta and its second within the Novartis kidney disease portfolio since August 2024, when Fabhalta was granted accelerated approval by the FDA for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Continued approval for this indication is contingent upon confirmatory evidence. Fabhalta received its first FDA approval in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Discovered by Novartis, Fabhalta is also being studied in a broad range of other rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications.

In addition to Fabhalta, Novartis is advancing the late-stage development of two additional IgAN therapies with highly differentiated mechanisms of action: atrasentan, an investigational oral endothelin A receptor antagonist that received FDA filing acceptance in Q2 2024 with a decision anticipated in H1 2025, and zigakibart, an investigational subcutaneously administered anti-APRIL monoclonal antibody that is currently in Phase III development.