The FDA approved sacubitril/valsartan, a twice-daily oral medication to treat patients with heart failure and reduced ejection fraction. The drug (Entresto, Novartis) was reviewed under the FDA’s priority review program and was granted a fast track designation.
Patients with New York Heart Association (NYHA) class II to IV heart failure will be eligible to receive the medication typically along with other therapies such as beta blockers to reduce the risk of death and heart failure hospitalization. Novartis mentioned in a news release that 2.2 million people in the U.S. have NYHA class II to IV heart failure.
Scott D. Solomon, MD, a study co-author and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, said sacubitril/valsartan cannot be used in combination with ACE inhibitors or ARBs because of an increased risk for angioedema.
Valsartan is an ARB that has been used for several years to treat heart failure and hypertension, while sacubitril is a neprilysin inhibitor. There are no other angiotensin receptor–neprilysin inhibitors currently approved in the U.S.
“This will be in place of an ACE inhibitor or an ARB, which have been the bedrock, gold standard of care for patients with heart failure for many, many years,” Solomon told Cardiovascular Business. “I think people will take (sacubitril/valsartan) when they consider that this drug not only makes people live longer with heart failure, it keeps them out of the hospital.”
The approval was based on results of the PARADIGM-HF study, which enrolled 8,442 patients. In March 2014, the Data Safety and Monitoring Board stopped the trial early because sacubitril/valsartan significantly reduced the risk of cardiovascular mortality compared with enalapril, which is a commonly used FDA-approved ACE inhibitor.
Patients who received sacubitril/valsartan had a 20 percent reduced risk for death from cardiovascular causes, a 21 percent reduced risk for heart failure hospitalizations and a 16 percent reduced risk for all-cause mortality compared with patients in the enalapril group.
“You can’t ever really anticipate such good results,” Solomon said. “This was really one of the most impressive results that we’ve had in heart failure in over a decade.”
During PARADIGM-HF, most patients also received other FDA-approved treatments such as beta-blockers, diuretics and mineralocorticoid antagonists. Common side effects associated with sacubitril/valsartan included hypotension, hyperkalemia and renal impairment.
Solomon said patients who received sacubitril/valsartan had fewer increases in potassium or creatinine, which are two reasons doctors stop prescribing ARBs or ACE inhibitors.
Based on the results of PARADIGM-HF, the FDA did not convene an advisory committee when assessing sacubitril/valsartan. The approval came six weeks earlier than the FDA's priority review action date, which was in August. Novartis expects sacubitril/valsartan to be available at pharmacies within a few weeks.
“There was a public health imperative to get this on the market as soon as possible,” said Solomon, who is also a professor at Harvard Medical School who specializes in heart failure and cardiac imaging. “The fact that (the FDA) was able to move quickly is a testament to the strength of the data. This trial was the largest heart failure trial yet done, so we certainly had an enormous amount of support for the indication.”