Novartis' Heart Failure Drug Poised To Earn Blockbuster Status

Novartis posted top-line, positive results from its much-awaited PARADIGM-HF study showing that its investigational heart failure drug LCZ696 cut 20 percent of cardiovascular deaths and hospital admissions.

LCZ696 is a twice-a-day tablet under investigation as a treatment for heart failure. The drug is an ARNI (Angiotensin Receptor Neprilysin Inhibitor) that works to reduce the strain on a patient’s failing heart. LCZ696 recruits the body’s own defenses and simultaneously enhances levels of endogenous vasoactive peptides while inhibiting the renin-angiotensin-aldosterone system (RAAS).

In the double-blind, randomized Phase III study, LCZ696 showed superiority to ACE inhibitor enalapril. Novartis reported that the drug reduced the risk of cardiovascular-related death by a fifth or fully 20 percent of patient subgroups in the study. LCZ696 also cut down hospital admissions due to heart failures by 21 percent. In addition, Novartis’ investigational drug also reduced the risk of all-cause mortality by 16 percent.

David Epstein, Division Head of Novartis Pharmaceuticals, said, “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.”

An estimated 26 million people across the U.S. and EU suffer from risk of heart failure and face the threat of death and poor quality of life. Based on its high performance, Reuters projects LCZ696 will be a multi-billion dollar blockbuster thanks to its anticipated high price tag. “Given the survival advantage of LCZ696 over currently available drugs, once this drug becomes available, it would be difficult to understand why physicians would continue to use traditional (drugs) ... for the treatment of heart failure,” said Milton Packer of the University of Texas and joint-principal investigator on the PARADIGM-HF study.

However, medical journalist Larry Husten was cautiously optimistic about labeling the drug as a ‘blockbuster’ in a previous article in Forbes. He cites the case of Bristol-Myers Squibb’s omapatrilat as an example. Omapatrilat was a drug similar to LCZ696 that was found to induce angioedema. While Novartis’ drug has yet to show signs of inducing angioedema, Husten cautions that there is no such a thing as a sure thing, especially when it comes to heart failure drugs.

The company said it expects to file regulatory applications for the drug in the U.S. by the end of the year and in the EU early next year.