The prevailing theory of how to treat Alzheimer’s disease endured its 1,001st cut on Thursday, as results from a lengthy clinical trial showed that reducing toxic plaques in the brain had no effect on slowing cognitive decline.
While the disappointing result is only the latest in a metronomic series of failures, it could have implications for the drug industry’s only ostensible success: a plaque-targeting treatment from Biogen soon to undergo Food and Drug Administration review.
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One can’t ignore the fact that there have been many clinical failures of anti-ABeta approaches. But the article just piles onto the “Amyloid Hypothesis is Dead” bandwagon by rehashing the old news (failure to improve cognition, announced last year) and ignoring the new Ganternerumab data. The cognition effects of Gantenerumab were measured early on and before the dose was raised. Whereas the biomarker responses were measured after longer exposure to drug and at much higher doses. The biomarker responses for Gantenerumab show an UNPRECEDENTED consistency across all parameters, and the burning question is whether they would translate into a cognitive benefit. But unfortunately cognition was measured at a completely different, earlier time point. We simply do not know what the effect would have been on cognition after longer and higher dosing.
The prevailing theory of how to treat Alzheimer’s disease endured its 1,001st cut on Thursday, as results from a lengthy clinical trial showed that reducing toxic plaques in the brain had no effect on slowing cognitive decline.
That’s not the prevailing hypothesis, and it has not been for nearly 20 years. Plaque formation occurs late in disease progression, but accumulation of amyloid protein occurs early in the disease. You can detect this accumulation before symptoms of AD occur using PET imaging and the florbetapir radiotracer. That’s why Lilly spent a billion dollars buying the company that developed florbetapir, so they could detect presymptomatic cases and treat them with solanezumab before the disease really gets going. The fallback position after the failure of the first two Phase III clinical trials and re-analysis of a subset of the data was they hadn’t started treatment soon enough, and maybe by identifying suitable subjects earlier they would have success with solanezumab by stopping amyloid accumulation long before the brain damage and plaque formation occur. Solanezumab and the other amyloid antibody drugs are intended for this purpose, not really for preventing plaque formation by which time the train has already left the station.