Lilly Leads Late-Stage Development of AD Drugs
While reviewing trials of novel agents for Alzheimer disease at the NIH database, one thing is readily apparent: There are few candidates in the late-stage pipeline.
With 2 drugs in phase 3 development, Lilly is the clear frontrunner. Its sole competition appears to be a green tea extract, sunphenon EGCg, which is being assessed in 1 actively recruiting, phase 2/3 AD trial in Germany.*
Lilly’s drugs of promise are semagacestat (LY450139), a gamma-secretase inhibitor, and solanezumab (LY2062430), a monoclonal antibody. For what it’s worth (and that may not be much), both are intended to disrupt or break up the amyloid plaques of AD (like the woebegone bapineuzumab).
Two phase 3 company-sponsored trials of semagacestat are listed in the NIH database (here and here). The first trial, called IDENTITY, will be completed in June of next year. And two phase 3 trials of solanezumab, EXPEDITION and EXPEDITION 2, are recruiting patients with mild-to-moderate AD (here and here). These trials will not be completed until 2012.
A phase 2 safety trial of semgacestat in 51 patients with mild-to-moderate AD revealed possible “concerns” about skin and hair reactions. Although plasma levels of amyloid beta dropped significantly with semagacestat, there were no treatment-related changes in CSF levels and no between-group differences in cognitive measures; however, the trial was too short (14 weeks) to adequately assess any cognitive benefits. A more recently published study showed that single doses of semgacestat reduce amyloid beta production, but not clearance, in a dose-dependent fashion.
* The trial is expected to be completed in April of 2011.
Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.