Comments on: The Betting On Wyeth & Elan’s Alzheimer’s Drug

By: Nathan

Nathan — Tue, 29 Jul 2008 17:48:32 +0000

Jeffrey - That’s a great question - I was wondering the same thing myself. I guess that the report did not promote pessimism around bapineuzumab because bapineuzumab had already shown a hint of efficacy. (as in the press release last month) Ultimately, the validity of the amyloid plaque hypothesis is irrelevant. What matters is efficacy — regardless of mechanism. There are many drugs that have been designed with a particular hypothesis in mind. The products work, but then the underlying hypothesis is disproven by some other scientific work. Later, it’s found that the drugs seem to work by a completely different mechanism than what was originally intended. Many CNS drugs and cancer drugs that are on the market fall into this category. There is WAY more serendipity in drug discovery than we like to admit.

By: Jack2

Jack2 — Tue, 29 Jul 2008 17:44:43 +0000

Flurizan is a small molecule that hopefully reduces the generation of the protein (A-Beta) that forms the plaques. It blocks the enzmes that makes A-beta. The hope here is to stop/reduce plaque formation.

Secondarily, the drug could promote plaque clearance. It’s possible the plaques always exist in a dynamic equilibrium, with some plaques breaking down and others forming. In a patient with AD, the equilirium gets shifted towards the plaques. If you stop a patient from making new plaques, then the existing ones might breakdown.

Bapineuzumab is an antibody that targets A-Beta. It hopes to promote clearance (probably immune-system mediated clearance) of plaques. It’s easier to see how this drug could potentially more directly target existing plaques, and help someone with existing disease, rather than just preventing progression.

I think Merck has a drug like bapin., and it failed, not because of lack of efficacy - but because of safety. Patients suffered an immune reaction in their CNS.

Of course, it is possible these treatments are misguided, and A-beta plaques are just a symptom of AD (or even a protective mechanism), and modulating plaque formation will not help AD symptoms (and maybe even worsen it).

However, *most* evidence points to A-beta plaques (along with, possibly, tangles of another protein - tau), as the major culprit in the disease. The three hallmarks of AD are A-beta plaques, tau tangles, and neuronal loss. It’s certainly the best available lead.

bapineuzumab

By: Jeffrey Clark, CEO of Beaker.com - The Online Community for Life Sciences Professionals

Tue, 29 Jul 2008 17:07:52 +0000

I need a scientist on this blog to help me understand. Less than a month ago, Myriad Genetics stopped developing Flurizan.

From the NY Times:

“The failure is significant because Flurizan was one of the first drugs to reach late-stage testing that was seen as working by trying to prevent the buildup of toxic amyloid plaques in the brain. Such plaques are the focus of the leading theory for the cause of Alzheimer’s disease. The drug’s failure might cast some new doubt on that theory as well as on other experimental drugs to block amyloid plaques. That treatment focused on amyloid plaques in the brain, the current popular target as to the cause of ALZ.”

So why has this not caused great pessimism around the potential of the treatments from Elan/Wyeth & Lilly that focus on the same root cause of the disease? While they may have a unique mechanism of action, from what I can tell, both focus on amyloid plaque as the culprit when Myriad’s results hint that may not be the case.

By: Nathan

Nathan — Tue, 29 Jul 2008 14:59:10 +0000

42% of ~30 million people is still a HUGE number. Considering the lack of effective treatments, even if it was only effective in 10% of patients, it could still be a major blockbuster.

By: Chris

Chris — Tue, 29 Jul 2008 14:30:23 +0000

Farrer et al. 1997 JAMA 278:1349 found that about 58% of AD patients are ApoE4 carriers. So if it works in non-carriers but not in carriers, the majority of patients would not benefit.