October 15, 2014 — Novartis Pharmaceuticals Canada Inc. revealed, in the largest heart failure study to date, that its investigational heart failure medicine, LCZ696, was superior to the ACE-inhibitor enalapril on key endpoints. The results were released at the 2014 European Society of Cardiology (ESC) Congress and published simultaneously in the New England Journal of Medicine.
In PARADIGM-HF, patients with heart failure and reduced ejection fraction (HF-REF) who were given LCZ696 were more likely to remain alive and have less re-hospitalization for heart failure than those given the ACE-inhibitor enalapril. Patients received LCZ696 or enalapril combined with the current best treatment regimen for heart failure treatment. The safety and efficacy of LCZ696 is still under investigation, and market authorization has not yet been obtained in Canada.
"The results of the PARADIGM study showed a reduction in hospitalizations for heart failure, a reduction in cardiovascular mortality and a reduction in total mortality when added to optimal therapy. It also improved the quality of life of patients in the trial," said cardiologist Jean-Lucien Rouleau, M.D., of the Montreal Heart Institute, a member of the PARADIGM-HF executive committee and a co-author of the study article. "These results are important given that one in every five or six of the Canadian population, over the age of 40, will experience heart failure. The PARADIGM-HF results are promising and may have a major impact in the way we manage heart failure in the future."
The PARADIGM-HF results showed the investigational treatment LCZ696, when added to current optimal care and compared to adding the ACE-inhibitor enalapril to optimal care, reduced:
- the risk of death from cardiovascular causes by 20 percent (p=0.00004);
- heart failure hospitalizations by 21 percent (p=0.00004); and
- the risk of all-cause mortality by 16% (p=0.0005).
Overall there was a 20 percent risk reduction on the primary endpoint, a composite measure of CV death or heart failure hospitalization (p=0.0000002).
"Given the increasing prevalence, the high hospitalization rate and mortality in heart failure, there is a great need for new treatment alternatives in Canada and around the world,'' said Jean Godin, M.D., chief scientific officer and vice president, clinical and regulatory affairs, Novartis Pharmaceuticals Canada. "These results show the importance of pursuing research and development efforts to further improve the health outcomes of patients affected by this condition."
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 while simultaneously suppressing the RAAS system.
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 percent versus 12.3 percent, 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 pursue filings for marketing authorizations in different jurisdictions around the world, starting late in 2014 and continuing in 2015.
For more information: www.novartis.com