Novartis has secured US Food and Drug Administration (FDA) approval for Fabhalta (iptacopan) as the first authorised treatment for adults with C3 glomerulopathy (C3G), a rare and progressive kidney disease.
The approval allows Fabhalta to be used to reduce proteinuria in affected patients, providing a new treatment option where none previously existed.
Novartis US president Victor Bultó said: “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.”
Fabhalta is an oral inhibitor targeting the alternative complement pathway, a key factor in the progression of C3G. Until this approval, patients relied solely on supportive care, broad immunosuppressive therapies, and symptom management.
C3G typically presents in young adults, with an average diagnosis age of 23 years. The condition significantly impacts kidney function, and around half of those diagnosed progress to kidney failure within a decade, requiring dialysis or a transplant.
Patients often experience fatigue, mobility issues, and mental health effects, including depression and anxiety.
The FDA’s decision follows findings from the Phase III APPEAR-C3G trial, which assessed Fabhalta’s efficacy and safety.
The study included a six-month randomised, double-blind treatment phase, comparing Fabhalta to a placebo alongside standard supportive care. This was followed by an additional six-month open-label period in which all participants received Fabhalta.
Results showed a clinically significant reduction in proteinuria, with improvements observed as early as 14 days and sustained at 12 months. Patients who transitioned to Fabhalta during the open-label phase also experienced similar benefits.
Fabhalta demonstrated a favourable safety profile, with no new safety concerns reported. The most common adverse reactions, occurring in at least 10% of patients, included nasopharyngitis and viral infections.
Due to the risk of serious infections caused by encapsulated bacteria, Fabhalta is available only through a Risk Evaluation and Mitigation Strategy (REMS) programme, requiring specific vaccinations.
Beyond the US approval, Novartis is pursuing additional regulatory clearances. Last month, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for Fabhalta’s use in C3G, while reviews are ongoing in China and Japan.
This marks Fabhalta’s third FDA approval, following its December 2023 authorisation for treating paroxysmal nocturnal haemoglobinuria (PNH) and its August 2024 accelerated approval for reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression.
Continued approval for IgAN remains subject to confirmatory data.
Novartis is further investigating Fabhalta’s potential in other rare kidney diseases, including atypical haemolytic uraemic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN). Clinical trials are ongoing to assess its safety and efficacy in these indications.
Alongside Fabhalta, Novartis is advancing two additional investigational therapies for IgAN. These include atrasentan, an endothelin A receptor antagonist expected to receive an FDA decision in the first half of 2025, and zigakibart, a subcutaneous anti-APRIL monoclonal antibody currently in Phase III trials.
