Few drugs in Novartis' ($NVS) pipeline loom larger than LCZ696, a heart failure med that has singlehandedly saved the pharma giant's cardio drug development strategy from the embarrassing setback triggered by serelaxin's big flop on the regulatory front. So now that a group of researchers are suggesting that the drug could--as in maybe, conceivably but certainly not for sure--be linked to accelerating Alzheimer's, the new research is getting some very careful scrutiny.
Forbes contributor Larry Husten, who specializes in all things cardiovascular, was quick to pick up on the implications with his own close review of the case--for and against. The French researchers zeroed in on sacubitril, an essential ingredient of LCZ696 which inhibits neprilysin with a tonic effect on hypertension. Novartis recently ended a big study of the drug early on very promising results. But the researchers say that neprilysin attacks amyloid beta, the toxic protein that many researchers believe is the likely cause of Alzheimer's. Hit this target, they say, and you run the risk of accelerating the memory-robbing disease among an at-risk population by allowing brain-damaging clusters to form more rapidly.
The big study on LCZ696, PARADIGM-HF, didn't find evidence of cognitive decline, these researchers add, according to Husten's account, but it also wasn't closely studied. And the follow-up study may be insufficient to expose any such declines in patients. The researchers also highlight that the other essential ingredient in LCZ696 could help with Alzheimer's.
While there are plenty of clues being researched as to what causes Alzheimer's, it should also be noted that there's no scientific certainty about it. Biopharma companies have spent billions of dollars pursuing the amyloid beta theory and other ideas, but over the last decade R&D programs have run a near-100% failure rate.
Being a thorough reviewer, Husten tracked down Milton Packer, the co-principal investigator involved in PARADIGM-HF.
"Fortunately," he told Forbes, "we have actual data from long-term clinical trials (not only PARADIGM-HF but also OVERTURE), showing no increase (and actually a decrease) in dementia-related adverse events in patients receiving long-term treatment with neprilysin inhibitors." Husten explains that OVERTURE tested omapatrilat, a similar therapy that failed for reasons unrelated to Alzheimer's.
That decrease in dementia-related events, Packer added, could be linked to the vascular effect linked to the drug, which may be one of many factors that contribute to the development of Alzheimer's.
Husten raises the possibility that if any signal related to an adverse neurocognitive effect is flagged in upcoming data on the drug, Novartis could find itself being forced to defend the drug. And with analysts pegging peak annual sales of this drug in the billions, any potential threat to this franchise will be followed closely by analysts.
- here's the analysis from Forbes