BioCentury
ARTICLE | Product Development

Alzheimer's rewind

Gamma secretase woes in Alzheimer's prompt search for alternative targetsNext Phase III data in AD will come from beta amyloid mAbs in 2012

October 24, 2011 7:00 AM UTC

A string of Phase II and III failures in Alzheimer's disease has prompted companies to look for new targets beyond the well-known players in the core mechanism of AD - the production and accumulation of beta amyloid deposits in the brain. The next wave of candidates includes more than 20 clinical stage small molecules for targets that indirectly affect beta amyloid production and/or toxicity, or aim for solutions that might be disease-modifying even as they ameliorate symptoms.

Among the latest casualties are gamma secretase inhibitors, which first entered the clinic more than a decade ago. The two most advanced molecules, one in Phase III and one in Phase II, have shown safety signals that suggest the basic approach to the target will need to be refined. A handful of clinical and preclinical programs aiming to create a second generation of molecules are already underway...