The US FDA has approved Novartis’ blockbuster-in-waiting Entresto to reduce the risk of cardiovascular death and hospitalisations in heart failure (HF) patients.
The green light for Entresto (sacubitril and valsartan) is the first anywhere in the world for the first-in-class neprilysin inhibitor and comes several weeks ahead of the review deadline, having been awarded both a priority review and fast-track designation by the US regulator. Novartis has said it intends to launch the product within the next few days.
The approval for the drug – formerly known as LCz696 – was backed by data from the PARADIGM-HF trial, which showed the drug cut cardiovascular deaths by 20% versus standard therapy based on the ACE inhibitor enalapril, while also reducing hospitalisations by 21% and all-cause mortality by 16%.
With trials showing enalapril can improve survival by around 15% in HF, the trial showed that Entresto could more than double survival compared to this widely used, standard therapy for the disease. That improvement was particularly remarkable given that patients in the trial were also being treated with background therapy for HF including beta-blockers, diuretics, and mineralocorticoid antagonists.
“Heart failure is a leading cause of death and disability in adults,” said Norman Stockbridge, who heads the FDA’s Division of Cardiovascular and Renal Products. “Treatment can help people with heart failure live longer and enjoy more active lives,” he added, noting that there are around five million people with HF in the US.
Novartis notes that Entresto will be suitable for around half the patients with HF in the US – those with reduced ejection fraction – and estimates the product could eventually grow into a $5bn-a-year brand. If its indications are expanded in future to include other HF types – such as patients with preserved ejection fraction – peak revenues could be even higher, it suggests.
Despite the compelling clinical data Entresto is also launching into a market dominated by low-cost generic medicines, however, and Novartis has already indicated it would consider a novel risk-sharing pricing strategy in which payment for the drug would be based on clinical outcomes rather than tablet sales.
“Despite the uncertainty and high financial risk we designed the world’s largest heart failure trial to compare Entresto to the previous gold standard,” commented David Epstein, the company’s head of pharmaceuticals.
“As a result millions of people diagnosed with reduced ejection fraction HF now have a much greater opportunity to live longer and stay out of hospital.”
Entresto was also the first product to be granted an accelerated review by the European Medicines Agency (EMA), which is currently reviewing the application.