Novartis has shared positive results from a late-stage trial of its factor B inhibitor Fabhalta (iptacopan) in patients with the ultra-rare kidney disease complement 3 glomerulopathy (C3G).
Approximately one to two people per million worldwide are diagnosed every year with C3G, which occurs when an over-activation of the alternative complement pathway causes deposits of C3 protein to build up in kidney glomeruli.
This triggers inflammation and glomerular damage that results in proteinuria (protein in urine), haematuria (blood in urine) and reduced kidney function, with about 50% of C3G patients progressing to kidney failure within ten years of diagnosis.
The ongoing phase 3 APPEAR-C3G study has been evaluating the safety and efficacy of a twice-daily 200mg dose of Fabhalta in C3 patients.
Results, which were presented at this year’s European Renal Association Congress, showed that patients treated with Fabhalta in addition to supportive care achieved a 35.1% reduction in proteinuria at six months, compared to placebo plus supportive care.
Data on the secondary endpoint of estimated glomerular filtration rate, a measure of kidney function, also showed improvements over six months with Fabhalta compared to placebo, and Novartis’ therapy demonstrated a favourable safety profile with no new safety signals observed.
APPEAR-C3G steering committee member, David Kavanagh, Newcastle University, said: “Fabhalta is the first potential treatment that targets the alternative complement pathway in C3G, and its impact on measures of kidney damage and kidney function in this study, in addition to its safety profile, is encouraging for patients and the clinical community.”
The trial will continue with an additional six-month, open-label period, in which all patients will receive Fabhalta, including those who were in the placebo cohort of the double-blind period.
Beyond C3G, Fabhalta is currently in development for a range of rare diseases, including IgA nephropathy, immune complex membranoproliferative glomerulonephritis, atypical haemolytic uraemic syndrome and lupus nephritis.
The therapy was approved by the US Food and Drug Administration in December to treat adults with the rare blood disorder paroxysmal nocturnal haemoglobinuria and received a positive opinion from the European Medicines Agency’s human medicines committee in March this year for the same patient population.
David Soergel, global head, cardiovascular, renal and metabolism development unit, Novartis, said: “The APPEAR-C3G results add to the growing body of evidence demonstrating Fabhalta’s potential to target the underlying pathophysiological drivers and to provide clinically meaningful outcomes in a range of rare conditions.”
