Novartis Tries to Debunk Possible Link Between Heart Failure Therapy and Alzheimer’s
A suggested link between Novartis’ heart failure drug LCZ696 and progression of Alzheimer’s disease could sour hopes of a pipeline replacement for the company’s failed Reasanz heart drug.
The link was highlighted in a January European Heart Journal article that noted opposite mechanisms of action of the drug’s active ingredient sacubitril in cardiovascular disease and in Alzheimer’s disease. Sacubitril lowers blood pressure by inhibiting an enzyme called neprilysin, but neprilysin is also needed to fight beta amyloid plaque buildup, the lead cause of Alzheimer’s.
The EHJ article stemmed from comments on a Phase III study of LCZ696 reported in the Sept. 11, 2014, New England Journal of Medicine article citing evidence that mice given the drug developed plaque buildups 30 to 50 times the normal level.
Novartis, which has suggested LCZ696 might fill a hole in its pipeline left by the failure of Reasanz (serelaxin) to win approval, is refuting a possible link.
Milton Packer, a cardiologist at the University of Texas Southwestern Medical Center and one of the principal investigators on Novartis’ studies of the drug, says an animal model isn’t reliable to accurately predict outcomes in humans. What’s more, LCZ696’s other component, an angiotensin receptor blocker called valsartan, has actually been shown to improve cognition in humans, he adds.
Novartis spokeswoman Julie Masow says the company followed 8,442 patients for up to five years in a Phase III study and found no evidence of cognitive impairment. The drugmaker ended that trial ahead of schedule last April, after a data monitoring committee determined there was substantial evidence that it met the primary endpoint of reducing death and heart failure hospitalizations.
Novartis has already submitted regulatory applications for the drug in the U.S. and EU, with the EMA’s Committee for Medicinal Products for Human use granting it accelerated assessment, Masow says. — Lena Freund