A new combination drug that could replace the “bedrock treatment” used to treat heart failure for more than 20 years is a step closer to becoming available across the European Union (EU).
The European Medicines Agency recommended sacubitril/valsartan (Entresto) for marketing authorisation on 25 September 2015, 11 weeks after it was fast-tracked for licence by the US Food and Drug Administration. Entresto is a combination of the angiotensin receptor blocker valsartan and the novel neprilysin inhibitor sacubitril.
The drug was recommended for an EU licence on the back of results of a randomised controlled trial involving more than 8,000 patients who had heart failure with reduced ejection fraction.
The patients were followed for a median of 27 months and the trial was stopped early when the results showed that Entresto was more effective than enalapril. Researchers found that 13.3% of patients treated with the combination drug died from cardiovascular disease compared with 16.5% taking enalapril, an angiotensin converting enzyme (ACE) inhibitor.
The trial also found that Entresto reduced the number of patients who had to be hospitalised for heart failure. The most common side effects of the therapy were hypotension, hyperkalaemia and kidney impairment, the EMA said. It has, however, decided to monitor its safety because of the potential risk of angioedema.
“The striking results in the PARADIGM-HF trial led me to believe that, once approved, [Entresto] could quickly replace what has been the bedrock treatment for more than 20 years, ACE-inhibitors,” says John McMurray from the University of Glasgow, a principal investigator in the trial.
He says the drug has the potential to extend the lives of “thousands” of patients as well as prevent hospital admissions.
Mike Knapton, associate medical director at the British Heart Foundation (BHF) charity, says: “This is a novel compound that improves outcomes in patients with heart failure by affecting the neurohormonal mechanisms that protect the heart – it inhibits neprolysin.”
Like all medicines, it is not suitable for everyone as it has significant side effects that need to be considered before recommending it, he says.
“Research, much of it funded by the BHF, has demonstrated that optimal treatment of patients with medications such as diuretics, ACE inhibitors and beta blockers, improves quality of life and reduces mortality,” says Knapton.
“The UK will now need to consider the role Entresto plays in the treatment of heart failure before the drug can be used here.”
The move towards achieving a market for Entresto in the EU comes at the same time as an ongoing debate in the United States about its price. Drug manufacturer Novartis is reported to be looking at introducing a novel price-fixing mechanism for the product whereby the drug would be offered at a discount initially but the price would rise if there is evidence that it has helped reduce costly hospital visits for heart failure patients.
The recommendation by the EMA’s Committee for Medicinal Products for Human Use now has to be ratified by the European Commission.