Novartis abandons Fabhalta trial in lupus nephritis

A failed phase 2 study has undermined Novartis' hopes of extending the approved indications for its oral complement inhibitor Fabhalta to include lupus nephritis.

According to an update on the clinicaltrials.gov registry website, Novartis has terminated the study of Fabhalta (iptacopan) as an add-on to standard therapy for patients with active class III to IV lupus nephritis, including patients with and without Class V membranous features of the autoimmune disorder, based on "strategic considerations."

The two-part study was assessing Fabhalta – with and without oral corticosteroids – in around 80 subjects with lupus nephritis, a serious form of kidney inflammation associated with the autoimmune disorder systemic lupus erythematosus (SLE). Around half of people living with SLE will develop lupus nephritis within five years.

The study started back in 2022, when the only approved therapies for lupus nephritis were GSK's injectable BLyS/BAFF inhibitor Benlysta (belimumab), cleared in 2020, and Otsuka's oral calcineurin inhibitor immunosuppressant Lupkynis (voclosporin), which reached the US market the following year.

Since then, Roche has secured FDA approval for Roche's anti-CD20 antibody Gazyva (obinutuzumab), which is also under review for SLE, and AstraZeneca got a green light for type I interferon receptor antagonist Saphnelo (anifrolumab), which have both made rapid headway into the lupus nephritis market.

Added to that, there is a clutch of other candidates coming through the industry pipeline for lupus nephritis and/or SLE, including Johnson & Johnson's FcRn blocker Imaavy (nipocalimab), Biogen's BDCA2-targeted litifilimab, and Merck KGaA's oral TLR7/8 inhibitor enpatoran, all of which are in late-stage clinical testing.

Novartis likely decided that the market has become too crowded for Fabhalta, which would have to play catch-up with its rivals.

The drug is already approved to treat three other disorders – blood disorder paroxysmal nocturnal haemoglobinuria (PNH) and rare kidney diseases primary immunoglobulin A nephropathy (IgAN) and complement 3 glomerulopathy (C3G) – and is one of Novartis' fastest-growing products, with sales rising 88% to $22 5 million in the second quarter of the year.

The company has previously projected peak sales of $3 billion-plus for Fabhalta – and potentially as much as $10 billion – depending on how many indications can be added to its label. Other trials are being run in atypical haemolytic uraemic syndrome (aHUS) and immune complex membranoproliferative glomerulonephritis (IC-MPGN).

News of the terminated trial was first reported in Endpoints.