09/07/2015
FDA Approves Entresto for Heart Failure Treatment
The FDA has approved sacubitril/valsartan (Entresto, Novartis) to treat heart failure (HF) with reduced ejection fraction.
The new oral drug is indicated for patients whose condition is classified New York Heart Association (NYHA) class II-IV to reduce the risk for cardiovascular death and hospitalizations due to HF. Entresto will replace an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, but will typically be used with other HF therapies.
“Heart failure is a leading cause of death and disability in adults,” said Norman Stockbridge, MD, PhD, the director of the Division of Cardiovascular and Renal Products in the FDA’s Center for Drug Evaluation and Research. “Treatment can help people with heart failure live longer and enjoy more active lives.”
In granting approval, the FDA considered the results from the 8,442-patient PARADIGM-HF study, which was stopped early when it was shown that Entresto significantly reduced the risk for cardiovascular death compared with the ACE inhibitor enalapril (N Engl J Med 2014;371[11]:993-1004). Most patients were also receiving β-blockers, diuretics and mineralocorticoid antagonists. Patients with reduced ejection fraction also experienced fewer hospitalizations due to HF. In the study, Entresto:
reduced the risk for death from cardiovascular causes by 20%;
reduced HF hospitalizations by 21%; and
reduced the risk for all-cause mortality by 16%.
Overall, there was a 20% risk reduction on the primary end point, a composite measure of cardiovascular death or time to first HF hospitalization.
Entresto is part of a new class of drug, called angiotensin receptor neprilysin inhibitors, which reduce the strain on the failing heart. Taken orally twice daily, it acts to enhance the protective neurohormonal systems of the heart while simultaneously suppressing the harmful renin-angiotensin-aldosterone system, which promotes left ventricular remodeling and contributes to left ventricular HF.
“The very meaningful survival advantage of Entresto seen in the PARADIGM-HF trial should persuade physicians to consider Entresto for all appropriate patients, in place of traditional ACE inhibitors or angiotensin receptor blockers,” said Milton Packer, MD, a professor and the chair of the Department of Clinical Sciences at the University of Texas Southwestern Medical Center, in Dallas.
An estimated 5.1 million individuals in the United States suffer from HF and about half have reduced ejection fraction. About 2.2 million of these individuals have NYHA class II-IV HF, based on how much their symptoms limit their physical activity. HF is a debilitating, life-threatening condition in which the heart cannot sufficiently pump blood around the body. Patients with HF face a high risk for death, repeated hospitalizations and symptoms such as breathlessness, fatigue and fluid retention, significantly decreasing quality of life.
The most common side effects of Entresto were hypotension, hyperkalemia and renal impairment. Angioedema was also reported; black patients and those with a prior history of angioedema have a higher risk. Patients should be advised to get emergency medical care immediately if they have symptoms of angioedema or trouble breathing while taking Entresto. Health care professionals should advise patients not to use Entresto with any drug from the ACE inhibitor class because of an increased risk for angioedema. When switching between Entresto and an ACE inhibitor, there should be a 36-hour washout period.
There is a possible risk for fetal harm, so Entresto should be discontinued in pregnant women.
Novartis said it would begin shipping Entresto next week.
