- The Food and Drug Administration on Tuesday approved broader use of Novartis' heart failure pill Entresto, a decision that will expand the number of Americans who can take the drug by about two-thirds, to as many as 5 million people.
- When first approved in 2015, Entresto could only be used in patients with "reduced ejection fraction," meaning their hearts are so weak they can only pump 40% or less of the blood in the left ventricle, leading to symptoms like breathlessness. The FDA's latest OK extends approval to heart failure patients with "preserved ejection fraction," which means their hearts can pump out more blood but still less than normal.
- Entresto is now the first drug to be cleared for both patient groups. U.S. treatment guidelines recommend doctors consider beta blockers and ACE inhibitors in some patients with preserved ejection fraction, although those drugs haven't been shown to prevent death or hospitalization.
Drugmakers have had a harder time turning newer cardiovascular drugs into the top-sellers that past medicines like Pfizer's Lipitor became. Entresto is no exception, as Novartis spent considerable resources to boost an initially sluggish launch.
Those efforts have paid off: Entresto is now the Swiss pharma company's third biggest drug with $2.5 billion in sales last year, a number 44% higher than 2019's sum.
On that trajectory, Entresto may soon surpass Novartis' number two product, the multiple sclerosis pill Gilenya, as soon as this year. The drugmaker expects the new approval could add $1 billion to peak annual sales for the drug, which it currently forecasts to be between $4 billion and $5 billion.
Novartis cautioned, however, that those numbers will be affected by inclusion of Entresto in physician guidelines for treatment of preserved ejection fraction patients and other factors.
"We're still operating in a COVID environment at least in the first half of this year," said Rod Wooten, Novartis' global marketing head, in a call with analysts on Wednesday. "Guidelines are a major driver, and as we've learned in the [reduced ejection fraction] population, it's just going to take time for this evidence to be evaluated [by physicians] and create some of that clarity in the marketplace."
In December, an FDA advisory committee voted 12-1 in favor of approving Entresto in this new group of patients based on results from the PARAGON-HF trial, which failed to meet its primary goal of significantly reducing heart failure hospitalizations and cardiovascular death when compared to valsartan, one of the active ingredients in Entresto.
But the panel decided the totality of evidence, which included fewer hospitalizations when measured separately from death as well as improvement in patient symptoms, was sufficient to support approval.
The FDA's OK gives Novartis first-mover advantage in a patient group with fewer options, and the company may not face competition for some time. Developing drugs for cardiovascular disease is proving to be increasingly difficult.
The cost of the huge trials necessary to win approval means that generally only big pharma can afford to run them. Insurers, meanwhile, are demanding the higher prices of new drugs be justified by improvement in patient outcomes over existing therapies, which often are lower-cost generics.
Cholesterol-lowering drugs from Amgen and Regeneron and Sanofi, for instance, struggled to make headway until the companies cut their prices. While the treatments powerfully reduce cholesterol, studies showed they are only modestly more effective than older drugs like Lipitor in preventing cardiovascular death and hospitalizations.
Regeneron last week won approval of a new cholesterol drug, called Evkeeza, for people a rare, genetic form of heart disease. The biotech set an average list price of $450,000 per year.
Entresto could face some competition from a generic drug, however. The same group of FDA advisers that supported Entresto's approval also recommended, by a closer 8-4 vote, clearance of the diuretic spironolactone the very next day.
Their decision was similarly based on a trial that missed its primary goal of reducing heart failure hospitalizations and cardiovascular death, but showed a benefit on reducing hospitalizations alone.