A trial of Novartis’ chronic heart failure drug LCZ696 has been halted prematurely after the drug was found to help patients live longer and avoid hospitalisation.
The PARADIGM-HF study – claimed to be the largest ever trial of a heart failure therapy – enrolled more than 8,400 patients with both heart failure and reduced ejection fraction (HF-REF), and compared twice-daily dosing of LCZ696 with the angiotensin converting enzyme (ACE) inhibitor enalapril, a standard therapy for these patients.
LCZ696 is the lead drug in the new angiotensin receptor neprilysin inhibitor (ARNI) class, which combines two mechanisms that should benefit HF patients in a single fixed-dose formulation, and has been tipped as a mega-blockbuster with sales of $5bn a year or more if it reaches the market.
The treatment combines Novartis‘ ACE inhibitor valsartan with an enzyme blocker called neprilysin, which boosts the activity of natriuretic peptides that can alleviate heart failure and some signs of cardiomyopathy.
The data monitoring committee for the PARADIGM-HF study had already indicated that the drug appeared to be safe in two earlier interim analyses, but decided to terminate the trial after “compelling efficacy” was indicated in the latest look at the data.
“The results of PARADIGM-HF are truly impressive,” said cardiologist Dr Milton Packer of Texas Southwestern Medical Centre in the US who was one of the principal investigators in the study.
The finding that treatment with LCZ696 was superior to current recommended treatment enalapril suggests the drug could become “a new cornerstone in the management of chronic heart failure,” he added.
The trial puts Novartis firmly on track to file for approval of LCZ696 in its first markets before the end of the year, suggesting it could be available as a treatment option for the 5 million-plus patients in the US and Europe who have HF-REF.
Given that a sizeable proportion of those patients are already on active therapy, the company has said in the past it believes its drug could be a candidate for around 3 million people in those markets.
The positive developments with LCZ696 for chronic heart failure contrast markedly with its acute heart failure therapy Reasanz (serelaxin), which was just rejected by the FDA advisory committee on the grounds of a lack of clinical evidence to support its efficacy.