FDA Approves Novartis' Fabhalta for Rare IgA Nephropathy

Novartis’ Fabhalta (iptacopan) has been granted accelerated approval by the US Food and Drug Administration (FDA) to reduce excess protein in the urine (proteinuria) of patients with the rare kidney disease immunoglobulin A nephropathy (IgAN).

Globally, around 25 individuals per million are diagnosed annually with IgAN, a condition where IgA protein accumulates in the kidneys, causing damage. This damage hampers the kidneys' ability to filter effectively, leading to substances such as blood and protein leaking into the urine. Despite available treatments, nearly half of IgAN patients with ongoing proteinuria progress to kidney failure within a decade to two decades after diagnosis.

Fabhalta, an oral factor B inhibitor of the alternative complement pathway, is previously approved in the US for treating the rare blood disorder paroxysmal nocturnal haemoglobinuria. The latest FDA approval targets patients at risk of rapid disease progression and is based on findings from the ongoing APPLAUSE-IgAN study. This study involves adult IgAN patients on a stable dose of maximally-tolerated renin-angiotensin system inhibitor therapy, with or without a stable dose of SGLT2i, receiving twice-daily oral Fabhalta.

Results from a pre-specified interim analysis of the phase 3 trial showed that patients treated with Fabhalta experienced a 38% reduction in proteinuria at nine months compared to those on a placebo. Additionally, the study indicated that Fabhalta was well tolerated, presenting a favorable safety profile consistent with previously reported data.

Victor Bultó, president of US operations at Novartis, highlighted this new approval as a significant milestone in their mission to transform rare renal disease care by providing new treatment options to those in dire need. Bultó emphasized their dedication to supporting individuals living with rare renal diseases and expressed enthusiasm for ongoing collaborations within this community as they continue to advance their portfolio.

Aligned with the FDA’s accelerated approval pathway, the continued authorization of Fabhalta may depend on the confirmation of clinical benefit from the APPLAUSE-IgAN study, which will further assess whether the therapy slows disease progression.

In addition to its application for IgAN, Fabhalta is also being developed to treat a variety of other rare conditions, including C3 glomerulopathy, immune complex membranoproliferative glomerulonephritis, atypical haemolytic uraemic syndrome, and lupus nephritis.