Harnessing the Alzheimer’s Pipeline

In today’s issue, we have a package about drugs in development to treat Alzheimer’s disease. The main piece looks at the different kinds of drug candidates targeting beta-amyloid, the peptide responsible for the plaques coating the brains of people with Alzheimer’s. Despite a slew of molecules in the later stages of development, there are still questions about whether blocking beta-amyloid accumulation makes the most sense. As the article says:

“If the trials are successful—and the amyloid hypothesis is proven true—doctors will have a slew of new drugs that could slow the progression of the disease. If the trials fail, scientists will be forced back to the drawing board to develop new hypotheses and drug targets.”

The second piece is a case study of the complicated chemistry campaign involved in developing Merck’s most advanced BACE inhibitor. BACE is an enzyme used to cut down a larger peptide into beta-amyloid, and it has proven to be a tricky target.

The last piece asks whether Dimebon, the drug candidate being developed by Medivation and Pfizer, has any legs left in it after it performed miserably in a Phase III trial. The companies say the jury is still out, while most neurologists have less kind words for the drug.

Overall, the stories try to harness the pipeline for a market in which big pharma is anxious to have a presence. In its pipeline review at the beginning of the year, Pfizer touted the 10 compounds in development for Alzheimer’s, making it the second only to oncology in terms of therapeutic focus. Bristol-Myers Squibb devoted a good portion of its R&D day last month talking about BMS-708163, its gamma-secretase inhibitor expected to head into Phase III trials later this year. And the number of basic patent filings for Alzheimer’s drugs has jumped from 652 in 2000, to 1995 last year, according to Chemical Abstract Services.

Why all the interest? The market is vast and patients are greatly underserved. The two Alzheimer’s drugs currently on the market, Pfizer’s Aricept and Forest Laboratories’ Namenda, are at best mildly effective at temporarily easing the symptoms of the disease. Last year, Pfizer sold $432 million worth of Aricept, while Namenda sales totaled $949 million. With 5.3 Americans suffering from Alzheimer’s, imagine the potential for a drug that actually slowed the disease down. Now factor in the potential for that number of afflicted to quadruple by 2020, and the market for an Alzheimer’s drug starts to look pretty huge. Add in the likelihood that for a drug to have the most effect, it’ll probably need to be given before dementia sets in and for the rest of a person’s life, and it starts to look ginormous.

Throughout the week, we’ll try to post some bonus commentary from our reporting for the stories. Let us know if there’s anything specific you want to hear about!

Author: Lisa Jarvis

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1 Comment

  1. I would be interested to hear about the disparity between Dimebon trials in Russia and the US; the Russian trials were remarkably positive, whereas the US trials were remarkably unremarkable.

    Also, the disparity in response between Pfizer/Medivation and the neurologists would be similarly interesting. Although have their own interests in mind, the opinion of a third party would be welcome. Is it wishful thinking on the part of Pfizer/Medivation?