Will gamma secretase Alzheimer's class survive the fall of semagacestat?

Date August 18, 2010

Eli Lilly’s failed trial for the Alzheimer’s drug, semagacestat, raises questions about whether the gamma secretase inhibitor class of compounds, and indeed the whole approach of targeting the beta-amyloid (A-beta) plaque, can reverse the course of the degenerative disease. Semagacestat is the second high profile failure of a gamma secretase candidate after Flurizan bombed out in similar fashion two years ago, indicating perhaps that inhibiting production of the amyloid precursor protein does not improve prognosis (Flurizan failure highlights Myriad's diagnostic potential, June 30, 2008).

The gamma secretase inhibitor class is, or was, regarded as promising and important in the battle to develop a disease modifying therapy for Alzheimer’s. While Lilly is hurting after this latest pipeline setback, hopes and attention now turn to the next most advanced candidates in the class (see table below), foremost of which is Bristol-Myers Squibb’s BMS-708163 - phase II data from a recently completed trial should be available by year-end and is now even more important for the gamma secretase approach to have a realistic future.

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