The multicentre, randomised, placebo-controlled APPLAUSE-IgAN trial recruited 518 adult patients with primary IgAN, who were given twice-daily doses of Fabhalta 200mg
Novartis announces positive data from Phase 3 trial of Fabhalta in IgA nephropathy treatment. (Credit: Novartis AG)
Novartis said that Fabhalta (iptacopan) has shown meaningful and statistically significant proteinuria reduction of 38.3% versus placebo as per pre-specified interim analysis of the Phase 3 APPLAUSE-IgAN study in patients with IgA nephropathy (IgAN).
Fabhalta is an investigational and oral Factor B inhibitor of the alternative complement pathway.
The multicentre, randomised, placebo-controlled APPLAUSE-IgAN trial enrolled 518 adult patients with primary IgAN, who were given twice-daily doses of Fabhalta 200mg.
The study has two primary endpoints for both interim and final analysis. First is the reduction of proteinuria at nine months, assessed through urine protein to creatinine ratio (UPCR) and second is the evaluation of the annualised total estimated glomerular filtration rate slope over 24 months.
Secondary endpoints, which include the proportion of participants achieving UPCR <1g/g without receiving other treatments, will also be evaluated in the final analysis.
The late-stage trial also revealed that Fabhalta had a good safety profile and was well tolerated, which is in line with previously published data.
Novartis renal and metabolism development unit cardiovascular global head David Soergel said: “IgAN progresses over many years, and patients’ needs may evolve such that different therapies may be best used at different times.
“Our renal pipeline includes medicines with a variety of mechanisms which may allow them to be targeted to patients based on their clinical characteristics.”
The US Food and Drug Administration (FDA) has accepted the submission for potential accelerated approval, and it is currently undergoing priority review.
At the completion of the study in 2025, the primary endpoint measuring the annualised total eGFR slope over 24 months will be used to assess Fabhalta’s ability to reduce the progression of IgAN.
Iptacopan is currently being developed for C3 glomerulopathy (C3G), atypical haemolytic uremic syndrome (aHUS), lupus nephritis (LN), and immunological complex membranoproliferative glomerulonephritis (IC-MPGN).
The FDA approved Fabhalta in December 2023 to treat people with paroxysmal nocturnal haemoglobinuria (PNH), a rare blood condition. In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) gave a positive opinion to the drug for the same indication.