The FDA this week gave early approval to Novartis drug Entresto, a combination pill consisting of valsartan (the generic of Novartis Diovan, an angiotensin blocker) and sacubitril, an inhibitor of the harmful protease, neprilysin. The drug is designed to reduce the toll of congestive heart failure (CHF).
CHF is among the most common causes of disability, hospitalization and death among Americans over age 65. Causes are manifold, most commonly CAD/MI, as well as hypertension and idiopathic cardiomyopathy (CHF of unknown specific cause). Nearly 5 million Americans are currently living with congestive heart failure (CHF). Approximately 550,000 new cases are diagnosed in the U.S. each year. Heart failure is responsible for 11 million physician visits each year, and more hospitalizations than all forms of cancer combined. CHF is the first-listed diagnosis in 875,000 hospitalizations, and the most common diagnosis in hospital patients age 65 years and older. In that age group, one-fifth of all hospitalizations have a primary or secondary diagnosis of heart failure. More than half of those who develop CHF die within 5 years of diagnosis. Heart failure contributes to approximately 287,000 deaths a year. Sudden death is common in patients with CHF, occurring at a rate of six to nine times that of the general population.
The approval was based in large measure on the study known as PARADIGM-HF, reported in the New England Journal of Medicine last September. In that study, a multi-center group of researchers led by Drs. John McMurray of the University of Glasgow, and Milton Packer of the University of Texas Southwestern Medical Center in Dallas, compared a control group of about 4,220 patients who were maintained on the ACE-inhibitor enalapril, to a similar group on the index therapy, Entresto. All patients were either somewhat disabled by congestive heart failure (NYHA Class II), or seriously impaired (Class III), or just about bedridden by CHF (Class IV). Other medications were permitted at the discretion of the treating MDs. Index outcomes were cardiac death or hospitalization for CHF. (Patients with NYHA Class IV CHF have a poorer prognosis than almost any cancer; their only hope for survival beyond one year given current therapies resides in the small possibility of a heart transplant).
The study was stopped early when referees determined that the active treatment group (Entresto) had a 20 percent lower incidence of the target outcomes (death or CHF deterioration) than the enalapril group. The treatment group had somewhat higher incidence of low blood pressure and allergic reactions, but none of these were deemed severe.
ACSH s director of medicine and public health, Dr. Gil Ross, had this perspective: This is clearly a groundbreaking report. There hasn t been a significant new drug for CHF in quite a while, perhaps 10 years, since the ARBs came along. The fact that this drug combination is priced at a fairly reasonable level Novartis estimates its annual cost will be about $4,500 makes it a potentially miraculous benefit for the 2.2 million Americans thought to be candidates for it now. Of course, it would be great to have another study or two to confirm this one.