Another Alzheimer’s drug bites dust

CHICAGO - Eli Lilly’s decision to pull the plug on Alzheimer’s drug semagacestat raises new questions about the long-held theory that removing clumps of a protein in the brain called amyloid beta or keeping them from forming will arrest the disease.

By (Reuters)

Published: Tue 17 Aug 2010, 11:48 PM

Last updated: Thu 2 Apr 2015, 9:50 AM

The drug’s failure in late-stage studies is another blow to a field of research that has been littered with disappointments.

· About 100 compounds are being explored in clinical trials, and some researchers fear too many high-profile failures will scare drug companies away from Alzheimer’s research.

· Semagacestat was one of a handful of Alzheimer’s drugs left in late-stage clinical trials, and a big worry among researchers is that maybe none of the drugs will work because they are being tested on patients whose brains are already wrecked by the disease.

· But the failure of Lilly’s semagacestat may have more to do with the way it worked. The company said it halted two clinical trials of the drug because patients’ thinking ability got worse and the drug increased the risk of skin cancer.

The drug is a gamma secretase inhibitor, which works by interfering with a key building block of beta amyloid, a toxic protein that forms sticky brain plaques in Alzheimer’s disease.

Scientists had feared that gamma secretase inhibitors might cause side effects because they interfere with a biological process called Notch signaling, which is needed in many other cellular functions.

· The implications of the Lilly drug failure might have been bigger if the problem had been with solanezumab, Lilly’s other drug in late-stage clinical trials. Solanezumab is a monoclonal antibody, an engineered immune system protein that attacks amyloid by different means.

Another monoclonal antibody in development is bapineuzumab, a joint effort by Pfizer Inc and Johnson & Johnson , and it has also had some trouble.

Bapineuzumab is a front-runner in the race for a therapy that can disrupt the course of the disease, but a mid-stage study in 2008 found it caused brain swelling in some people, and the companies have been having trouble getting patients to volunteer for their four phase 3 studies.

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