Entresto gets broader indication from the FDA

The FDA gave Entresto (sacubitril and valsartan) an expanded indication today that Novartis, the drug’s maker, heralded as making their product an appropriate treatment for more than 80% of Americans with chronic heart failure.

The FDA-approved label for the drug now reads that Entresto is “indicated to reduce the risk of cardiovascular deaths and hospitalization for heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction below normal.”

(Entresto is also indicated for the treatment of symptomatic heart failure with systematic left ventricular systolic dysfunction in pediatric patients ages one and older.)

The company press release says that “for the first time, there is a treatment with benefit for patients diagnosed with guideline-defined heart failure that includes both those with heart failure with reduced ejection fraction (HFrEF) and many with heart failure with preserved ejection fraction (HFpEF).”

About half of the 6 million Americans with heart failure have the type with reduced rejection fraction, according to Novartis, and half, the type with preserved ejection fraction but of those, roughly 2 million have left ventricular systolic dysfunction.

“Of the more than 6 million Americans suffering from chronic heart failure (CHF), approximately 5 million may be appropriate for treatment with Entresto,” says the company press release.

“This approval is a significant advancement, providing a treatment to many patients who were not eligible for treatment before because their ejection fraction was above the region we normally considered reduced. Until now, treatment for these patients was largely empiric,” said Scott Solomon, M.D., a professor at Harvard Medical School and one of the leaders of PARAGON-HF trial. “We can now offer a treatment to a wider range of patients who have an LVEF below normal.”

Solomon was the lead author of results from the PARAGON-HF trial published in the Oct. 24, 2019, issue of the New England Journal of Medicine that showed that Entresto did not lower the rate of hospitalizations for heart failure or death from cardiovascular causes among patients with preserved ejection fraction (45% or higher). However, Solomon and his colleagues noted that results did indicate a possible benefit in patients with an ejection fraction in the lower part of the range (45% to 57%) of those included in the study and also in women.

Entresto is a twice-a-day medication that works by boosting the natriuretic peptide system while inhibiting the harmful effects of the overactive renin-angiotensin-aldosterone system. Sacubitril is a neprilysin inhibitor, which has the effect of increasing beneficial peptides, and valsartan is an angiotensin receptor blocker (ARB) thereby damping the renin-angiotensin-aldosterone system.

Entresto comes in three doses. For adults, the starting dose is 49/51 mg that gets ramped up to a target maintenance dose of 97/103.