The corpse was already cold, but now it is well and truly buried: Researchers finally published the final results of the final clinical trial of Eli Lilly’s (LLY) experimental Alzheimer’s drug solanezumab. The bottom line — failure — has been known since Dr. Lawrence Honig of Columbia University unveiled the sad details at the 2016 Clinical Trials on Alzheimer’s Disease conference. But the reaction of outside experts, plus little asides in the New England Journal of Medicine paper, offer an intriguing glimpse into the sorry state of Alzheimer’s drug development:
What’s solanezumab?
It’s a monoclonal antibody that binds to beta-amyloid peptides and clears them from the brain, ideally before they form the fibrils that clump into the amyloid plaques that define Alzheimer’s. It doesn’t clear plaques themselves, nor restore the destroyed synapses or dying neurons that are responsible for disease’s catastrophic symptoms.
Why am I getting deja vu?
Probably because Lilly’s Phase 3 trials of solanezumab have been failing since 2012. The first two, Expedition and Expedition2, tried solanezumab in people with mild to moderate Alzheimer’s. It didn’t work, Lilly announced in 2012. But there was a hint of benefit in the mild Alzheimer’s group. So Lilly launched Expedition3, enrolling only people with mild disease. And they had to have amyloid, as shown by either brain imaging or the presence of beta-amyloid in cerebrospinal fluid. After all, if solanezumab works by removing beta-amyloid, it would presumably benefit only patients who have it, not those with other causes of dementia.
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I ‘ll check
Why does continued defense of the amyloid hypothesis remind me of the Black Knight from Monty Python’s Holy Grail who never gives the fight as limb after limb is severed?
Hope researchers figure this one out sooner, rather than later. Why isn’t there more focus on what inflammatory factors cause Alzheimer’s and other dementias, and identifying and remediating them, instead of trying to reverse the process without turning off the sources?
Hi there the link to the NEJM paper isn’t working for me — do you mind sending a different link? Thanks
We modified the link. Try this one: http://www.nejm.org/doi/full/10.1056/NEJMoa1312889
Pat Skerrett
STAT