Derek Lowe gives the rundown on Lilly's failure in the clinic with a gamma secretase inhibitor. This is big news because it casts serious doubt on the beta amyloid plaque hypothesis of Alzheimer's disease. Given that beta amyloid plaque has been a major target for drug development in Alzheimer's for several decades, and there are not many other promising leads, we are pretty much wondering what's next. The most promising news to come out of Alzheimer's research is a major collaboration effort among big pharma which we really do not see in industry too often. You can get a further overview of the graveyard of drugs in this area in Lowe's archives (he used to do research in Alzheimer's disease).
My main comment here is that this is a very expensive example of how assuming or hoping that correlation=causation can be, and not just in terms of money (although no one can ignore that billions have been spent chasing this hypothesis). The gamma secretase inhibitor did what it was supposed to do, which was block one of the enzymes that produce beta amyloid plaque, and the Phase 2 results seemed pretty good on that measure (which was pretty good, as most previous efforts ran afoul of other biological pathways or had other problems). However, the clinical outcome (cognitive decline) was worse in the treatment group than in placebo, which suggests either that beta amyloid is a byproduct of the Alzheimer's process, or even that beta amyloid is the body's response to another process. Who knows?
What now?! Back to the drawing board.