New heart failure medicine recommended for approval
by Pharmacy Life - Published on 28 September 2015
The European Medicines Agency (EMA) has recommended granting a marketing authorisation for
Entresto (sacubitril/valsartan) for the treatment of
adults with symptomatic chronic heart failure with reduced ejection fraction, a condition where the heart muscle does not contract effectively and less oxygen-rich blood is pumped out to the body. Around half of people with heart failure will have reduced ejection fraction.
Standard medicines used for patients with heart failure are angiotensin converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) if ACE inhibitors are not tolerated by the patient, in conjunction with beta-blockers and/or mineralocorticoid antagonists (MRAs). These medicines have been available for many years.
Entresto is a
combination of valsartan (an ARB) and sacubitril. Sacubitril is the first in a new class of medicines called neprilysin inhibitors. Entresto works in two ways – valsartan blocks the angiotensin II type-1 receptor, suppressing the harmful effects of angiotensin II on the cardiovascular system while sacubitril blocks an enzyme known as neprilysin to enhance the protective neurohormonal systems of the heart. Because of its mechanism of action
Entresto should not be given together with another ARB or with an ACE inhibitor.
The efficacy of Entresto compared with enalapril (an ACE inhibitor) was assessed in
one randomised controlled trial including over 8,000 adults with heart failure with reduced ejection fraction. Patients also received other heart failure medicines. Patients were included in the trial if they were able to tolerate treatment with Entresto, ie, they did not need to stop treatment with Entresto due to side effects during a run-in period before the start of the trial.
The trial was stopped early when it was found that
Entresto was more effective than enalapril in reducing deaths from cardiovascular disease. The patients were followed for a median of 27 months. During the follow-up period
13.3 per cent of the patients treated with Entresto died from cardiovascular disease compared with 16.5 per cent of the patients treated with enalapril. The trial also found that Entresto reduced the number of patients who had to be hospitalised for heart failure.
The
most common side effects reported with Entresto were
hypotension (low blood pressure), hyperkalaemia (abnormally high levels of potassium in the blood) and kidney impairment. Therefore, CHMP recommended that treatment should not be started in patients with low blood pressure or high potassium levels. A follow-up plan to monitor the safety of Entresto, including the risk of angioedema (swelling of the lips and throat), was agreed by the CHMP.