FDA Approves Heart Failure Drug That Comes With Survival Benefit
Earlier this week, the FDA approved sacubitril/valsartan, being sold as Entresto by Novartis, for the treatment of heart failure (HF). The medication is creating much excitement in the cardiology community, which has been waiting for a new “blockbuster” that could both benefit patients and spur additional innovation.
Following trial results demonstrating a reduction in cardiovascular death and HF hospitalization in patients with reduced ejection fraction, the drug—called LCZ696 throughout its development—was granted priority review and fast-track designation, gaining clearance on July 7, 2015.
“I think the approval is important for several reasons,” Mariell Jessup, MD, of the Hospital of the University of Pennsylvania (Philadelphia, PA), told TCTMD in an email. “First, the speed with which it was done [signals] a clear desire on the part of the FDA to bring promising new drugs to patients as soon as possible in a safe manner.
“Second, Entresto represents a drug that works in a different manner, inhibiting a pathway that was described many years ago but now has a potentially very important clinical relevance,” she continued. “And third, the success of this drug has seemingly opened the floodgates of research into other potential heart failure drug investigation, making it a very exciting next chapter in the heart failure arena.”
The drug, which combines a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (ARB; valsartan), is indicated for patients with chronic HF (NYHA class II-IV) and reduced ejection fraction. It is meant to be administered with other HF medications in place of an ACE inhibitor or ARB.
Approval was supported by the 8,442-patient PARADIGM-HF trial, which was presented at the European Society of Cardiology Congress in 2014 and simultaneously published online in the New England Journal of Medicine. Compared with the ACE inhibitor enalapril, sacubitril/valsartan lowered the rate of cardiovascular death or HF hospitalization (21.8% vs 26.5%; HR 0.80; 95% CI 0.73-0.87), as well as rates of each component of the composite endpoint.
The most common side effects seen in the trial were hypotension, hyperkalemia, cough, dizziness, and renal impairment. In addition, angioedema developed in 0.5% of patients taking sacubitril/valsartan and 0.2% of those taking enalapril.
“Just like [ACE inhibitors] and ARBs and [mineralocorticoid receptor antagonists], Entresto has the potential to save lives and reduce hospitalizations, but patients need to be monitored for adverse effects carefully,” Dr. Jessup said.
Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), told TCTMD in an email that “there is—understandably—a great deal of excitement in the heart failure community about a new therapeutic option. The reduction in mortality with this drug versus an ACE inhibitor appears to be a major advance.”
However, there remains some question about what impact the drug will have on clinical practice right away, he said. “I imagine the initial uptake will be modest, given physician unfamiliarity with the drug and issues of cost,” he said. “We also have to see how the drug performs in real-world populations, as opposed to the clinical-trial population, where it looked very good.”
As for cost, he added, “If [sacubitril/valsartan] really reduces heart failure hospitalizations in actual clinical practice, as it did in the PARADIGM-HF trial, insurance companies may be more likely to cover it without a large co-pay.”
Dr. Bhatt said he was not aware of any special considerations in the cath lab for patients taking the drug, which affects potassium levels and renal function, because electrolytes and kidney function are already tested in all patients.
US Food and Drug Administration. FDA approves new drug to treat heart failure [press release]. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm. Published July 7, 2015. Accessed July 9, 2015.
- Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi-Aventis, and The Medicines Company.
- Dr. Jessup reports no relevant conflicts of interest.