Heart Failure Compound LCZ696 Shows Promise in Phase III Trial
Study closes early after endpoints are met
The data monitoring committee (DMC) for the PARADIGM-HF trial has unanimously recommended early closure of the study, indicating that patients with chronic heart failure with reduced ejection fraction (HF-REF) who received the investigational compound LCZ696 (Novartis) lived longer without being hospitalized for heart failure than did those who received standard care with the angiotensin-converting enzyme (ACE) inhibitor enalapril.
Approximately half of patients with chronic heart failure have HF-REF.
Because the efficacy and primary safety endpoints of the PARADIGM-HF trial have been met, the study will close early. This follows two interim analyses that showed that the safety profile of LCZ696 was acceptable.
LCZ696, a twice-daily pill for heart failure, is a first-in-class medication that acts on the neurohormonal systems of the heart, blocking receptors that exert harmful effects while promoting protective mechanisms. Known as an angiotensin receptor neprilysin inhibitor (ARNI), LCZ696 is thought to reduce the strain on the failing heart, thereby 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.
The PARADIGM-HF trial was a randomized, double-blind, phase III outcome study evaluating the efficacy and safety profiles of LCZ696 versus enalapril in 8,436 patients with HF-REF. The primary endpoint was a composite of the time to first occurrence of either cardiovascular death or heart failure hospitalization. The trial was also designed to detect a significant difference in cardiovascular death. The study was initiated in December 2009 and is the largest clinical trial in heart failure ever conducted.
Heart failure continues to be a significant and growing public health concern. More than 20 million people have the disorder in the U.S. and Europe. The health-economic burden currently exceeds $45 billion worldwide.
Source: Novartis; March 31, 2014.