Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Entresto (sacubitril/valsartan), marking an important milestone towards becoming available in the EU. Pending final approval by the European Commission (EC) Entresto, previously known as LCZ696, will be available for the treatment of adult patients with symptomatic chronic heart failure and reduced ejection fraction (HFrEF).

"With the poor prognosis heart failure patients face - only half will be alive 5 years from diagnosis - the CHMP's endorsement of Entresto brings hope for HFrEF patients in Europe," said David Epstein, Division Head, Novartis Pharmaceuticals. "Already we're hearing about the benefits US doctors and HFrEF patients are experiencing with Entresto and hope to receive a final green-light from the EC soon."

The CHMP's decision, which follows previous US and Swiss approvals, is based on results from the 8,442-patient PARADIGM-HF study in patients with HFrEF, which was stopped early when it was shown Entresto significantly reduced the risk of cardiovascular death versus ACE-inhibitor enalapril. At the end of the study patients who were given Entresto were more likely to be alive and less likely to have been hospitalized for heart failure than those given enalapril. Analysis of safety data showed that Entresto had a similar tolerability profile to enalapril.

"The striking results in the PARADIGM-HF trial led me to believe that once approved LCZ696 could quickly replace what has been the bedrock treatment for more than 20 years, ACE-inhibitors" said Professor John McMurray of the University of Glasgow and one of two Principal Investigators. "Thousands of lives could be extended and hospital admissions prevented with LCZ696's unique ability to boost natriuretic peptides, heart-helpful hormones, while simultaneously inhibiting the RAAS system."

Heart failure is a highly debilitating, life-threatening condition in which the heart cannot pump enough blood around the body because the muscles of the heart become too weak or too stiff to work properly. As a consequence patients face a high risk of death, repeated hospitalizations and symptoms such as breathlessness, fatigue and fluid retention that significantly impact quality of life. Even though millions live with heart failure most people fail to recognize the symptoms, meaning many are misdiagnosed or incorrectly attribute the signs to growing older.

Entresto exhibits the mechanism of action of an Angiotensin Receptor Neprilysin Inhibitor that reduces the strain on the failing heart. A twice-a-day tablet, it acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (the RAAS).

Results from the 8,442 patient PARADIGM-HF study showed, versus enalapril, Entresto: reduced the risk of death from cardiovascular causes by 20%; reduced heart failure hospitalizations by 21%; reduced the risk of all-cause mortality by 16%.

Overall there was a 20% risk reduction on the primary endpoint, a composite measure of CV death or time to first heart failure hospitalization.

Fewer patients on Entresto discontinued study medication for any adverse event compared to those on enalapril. The Entresto group had more hypotension and non-serious angioedema but less renal impairment, hyperkalemia and cough than the enalapril group.