Novartis announced that the Data Monitoring Committee (DMC) unanimously recommended early closure of the PARADIGM-HF study, indicating patients with chronic heart failure with reduced ejection fraction (HF-REF) who received LCZ696 lived longer without being hospitalized for heart failure than those who received standard care with ACE-inhibitor enalapril. Based on the compelling efficacy and primary endpoint having been met, the trial will now close early. This follows two previous interim analyses that showed the safety profile of LCZ696 was acceptable.
"Novartis recognizes the huge global need for treatments that extend and improve the lives of people with heart failure and we believe LCZ696's unique mechanism of action could be transformative," said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. "This result is a demonstration of our commitment to developing innovative medicines that have an impact on the most important outcomes like cardiovascular mortality."
The results of PARADIGM-HF will be submitted to a major medical conference for presentation and Novartis will now initiate discussions with global health authorities regarding approval for marketing.
"The results of PARADIGM-HF are truly impressive" said Dr. Milton Packer, Professor and Chair for the Department of Clinical Sciences at University of Texas Southwestern Medical Center, Texas, USA and one of the two Principal Investigators. "The finding that treatment with LCZ696 was superior to currently recommended doses of enalapril has profound implications for the care of patients with chronic heart failure. We now have compelling evidence that supports LCZ696 as a new cornerstone in the management of chronic heart failure."
LCZ696, a twice a day pill for heart failure, is a first in class medicine that acts in multiple ways on the neurohormonal systems of the heart, blocking receptors exerting harmful effects while simultaneously promoting protective mechanisms. Known as an ARNI (Angiotensin Receptor Neprilysin Inhibitor) LCZ696 is thought to reduce the strain on the failing heart, promoting the ability of the heart muscle to recover.
LCZ696 is the second treatment being developed by Novartis for patients with heart failure, along with RLX030 (serelaxin) for acute heart failure.
PARADIGM-HF is a randomized, double-blind, phase III outcome study evaluating the efficacy and safety profile of LCZ696 versus enalapril (a widely used ACE inhibitor) in 8,436 patients with heart failure with reduced ejection fraction (HF-REF). The primary outcome is a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and the trial is also designed to be able to detect a significant difference in cardiovascular death. The study was initiated in December 2009 and currently is the largest clinical trial in heart failure ever undertaken.
Chronic heart failure is a progressive, debilitating disease where the heart is unable to pump enough blood throughout the body. Symptoms such as breathlessness, fatigue and fluid retention can appear slowly and worsen over time, significantly impacting quality of life. Approximately half of patients have the reduced ejection fraction form of the disease (HF-REF).