Today at the European Society of Cardiology congress and published simultaneously in the New England Journal of Medicine, Novartis revealed that its investigational heart failure medicine, LCZ696, was superior to ACE-inhibitor enalapril on key endpoints in the largest heart failure study ever done. In PARADIGM-HFpatients with heart failure with reduced ejection fraction (HF-REF) who were given LCZ696 were more likely to be alive and less likely to have been hospitalized for sudden deterioration of their heart failure than those given ACE-inhibitor enalapril.Patients received LCZ696 or enalapril on top of current best treatment.
The magnitude of benefit with LCZ696 against enalapril in HF-REF patients was highly statistically significant and clinically important. In the study, the benefit of LCZ696 was seen early, was sustained and was consistent across subgroups. LCZ696:
– reduced the risk of death from cardiovascular causes by 20% (p=0.00004)
– reduced heart failure hospitalizations by 21% (p=0.00004)
– reduced the risk of all-cause mortality by 16% (p=0.0005)
Overall there was a 20% risk reduction on the primary endpoint, a composite measure of CV death or heart failure hospitalization (p=0.0000002).
“By demonstrating a very significant reduction in cardiovascular deaths while improving Quality of Life, Novartis’ new heart failure medicine, LCZ696, represents one of the most important cardiology advances of the last decade,” said David Epstein, Division Head, Novartis Pharmaceuticals. “We want to thank leading cardiologists from around the world
for their collaboration with us and their determination in advancing this important new life saving therapy for heart failure patients.”
LCZ696, a twice a day tablet being investigated for heart failure, has a unique mode of action which is thought to reduce the strain on the failing heart. It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (the RAAS). Currently available medicines for HF-REF work only to block the detrimental effects. Despite existing therapies, the mortality rate remains very high with up to 50% of patients dying within 5 years of a diagnosis of heart failure. Approximately half of patients with heart failure have HF-REF.
Analysis of the safety data from PARADIGM-HF showed side effects were manageable in the study. Fewer patients on LCZ696 discontinued study medication for any adverse event compared to those on enalapril (10.7% vs 12.3%, respectively, p=0.03). The LCZ696 group had more hypotension and non-serious angioedema but less renal impairment, hyperkalemia and cough than the enalapril group.
Novartis plans to file the application for marketing authorization with the US FDA by the end of 2014 and in the EU in early 2015.