Novartis announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Fabhalta® (iptacopan), a first-in-class complement inhibitor designed to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. This condition is generally identified by a urine protein-to-creatinine ratio (UPCR) of ≥1.5 g/g. Fabhalta targets the alternative complement pathway in the immune system, which is believed to contribute to the development of IgAN when overactivated in the kidneys.
The accelerated approval was based on a pre-specified interim analysis of the Phase III APPLAUSE-IgAN study, which measured the reduction in proteinuria at nine months compared to a placebo. However, it is not yet confirmed whether Fabhalta can slow kidney function decline in IgAN patients. Continued approval may depend on further verification of clinical benefits from the ongoing Phase III study, with final data expected in 2025.
Professor Dana Rizk, a key investigator in the study, highlighted the progressive nature of IgAN and emphasized the importance of targeted treatments like Fabhalta in addressing the disease.
IgAN is a rare, progressive disease where the immune system attacks the kidneys, leading to inflammation and proteinuria. Around 25 people per million are newly diagnosed with IgAN each year, and the disease progresses differently in each patient. Despite current treatments, up to 50% of patients with persistent proteinuria may progress to kidney failure within 10 to 20 years, requiring dialysis or transplantation. Targeted therapies like Fabhalta offer hope for more effective treatment options.
The Phase III APPLAUSE-IgAN study evaluated the safety and efficacy of twice-daily oral Fabhalta (200 mg) compared to a placebo in adult IgAN patients on renin-angiotensin system (RAS) inhibitor therapy. The interim analysis showed a 44% reduction in proteinuria at nine months in the Fabhalta group, compared to 9% in the placebo group, demonstrating a significant 38% reduction. Fabhalta also showed a favorable safety profile, with common adverse reactions including upper respiratory infections, lipid disorders, and abdominal pain.
Fabhalta is part of Novartis’s broader commitment to addressing rare kidney diseases. The company is also advancing two other IgAN therapies in late-stage development: atrasentan, an investigational oral endothelin A receptor antagonist, and zigakibart, an investigational anti-APRIL monoclonal antibody.
Bonnie Schneider, Director and Co-Founder of the IgAN Foundation, emphasized the significance of this approval, offering new hope to those living with IgAN.
The APPLAUSE-IgAN study will continue to evaluate the long-term effects of Fabhalta on kidney function, with additional data expected in 2025.
Novartis’s work in nephrology spans over 40 years, beginning with the development of cyclosporine, and continues today with a broad portfolio aimed at preserving kidney function. Fabhalta is the first drug from Novartis’s renal pipeline to receive FDA approval, with further studies underway for additional rare kidney diseases.
