The Perils of Alzheimers Drug Development

Abstract

The present commentary is based on the thoughtful commentary by Becker and Greig (2008) in the August issue of Current Alzheimer Research, who describe a broken Alzheimer's disease drug development system. Their theme is that it is not the drugs that fail clinical trials but potentially sponsors and investigators who fail the drugs. They argue that “many current problems encountered in Alzheimer's disease drug development can be avoided by changing practices associated with drug development.” According to the authors, we fail to give candidate drugs a fair shake by not finding the right dose, not evaluating patients properly, not using quality controls over our data, not effectively modeling the disease, and not using effective research designs. They say sponsors and investigators fail drugs every which way. It is hard to argue that mistakes are uncommon in AD drug development and easy for us to cherry pick and choose favorite miscues. Becker and Greig with the help of a colleague at the investment firm Rodman and Renshaw identified 100 failed AD drug programs within which according to their analysis 30 compounds possibly showing initial efficacy failed in phase 3. They imply that some of these compounds could possibly have succeeded in phase 3 and been marketed. Given the various errors in development they express concerns that we can not know with adequate certainty whether drugs are failing or investigators are failing drugs. This broad indictment is hard to counter because there are examples for the truth of every point Becker and Greig raise. One or another drug development program has fallen short on one or more of the authors’ critical points (Schneider 2008a). In particular, they example the development programs for two drugs - metrifonate and phenserine – that they knew well as researchers, consultants or original inventors. Metrifonate was developed by the large pharmaceutical company Bayer, and phenserine by a defunct boutique biotech, Axonyx.