Fabhalta is first FDA-approved therapy for rare disease C3G
Novartis has a third FDA-approved indication for its oral therapy for complement-mediated diseases – Fabhalta – after getting a green light in ultra-rare kidney disease C3 glomerulopathy (C3G).
Fabhalta (iptacopan) is the first treatment approved for C3G, which mostly affects adolescents and young adults and can lead to kidney failure and the need for a transplant in around half of all patients within 10 years – with the disease in some cases continuing to attack the donated organ.
It has been approved after a priority review by the FDA, reflecting the pressing need for a treatment for C3G, which is diagnosed in one to two people per million worldwide per year.
The oral complement inhibitor is already used to treat primary immunoglobulin A nephropathy (IgAN) and paroxysmal nocturnal haemoglobinuria (PNH), with sales reaching $129 million in for full-year 2024, which Novartis said was a "solid, steady performance" and generated mainly from patients switching from other injectable complement therapies.
C3G is seen as a key indication to inject some additional momentum into the product, which it has said could eventually reach peak annual sales of around $3 billion. For comparison, PNH and IgAN affect around 10-20 and 25 people per million, respectively.
The approval follows positive results for Fabhalta in the phase 3 APPEAR-C3G study, on which patients with C3G treated with the drug on top of supportive care experienced clinically meaningful reductions in protein in the urine (proteinuria) – a marker for kidney damage – that were sustained for at least 12 months.
An open-label period of the study revealed that proteinuria reduction was seen in participants who switched to Fabhalta from other treatments used off-label, while an improvement in estimated glomerular filtration rate (eGFR) slope was observed after Fabhalta was started that appeared to reverse patients' earlier rapid declines.
"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 patient group C3G Warriors.
"To finally have an approved treatment – and one that can be taken orally – is something people with C3G have been waiting for," he added. "Today's approval brings new hope for me, my family, and so many others."
The approval is the first for Fabhalta in C3G worldwide, although, it has been recommended for approval in the EU and is also under review in China and Japan.
The drug is also in clinical trials for other rare kidney diseases, including atypical haemolytic uraemic syndrome (AHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis.
Other potential rivals in C3G include Apellis' C3 inhibitor Empaveli (pegcetacoplan), which recently generated positive phase 3 data, as well as Omeros Corp's antibody-based MASP-3 inhibitor zaltenibart, which is due to start phase 3 testing this year.
Photo by Robina Weermeijer on Unsplash
