Failed Verubecestat Trial May Call into Question Beta-amyloid Theory in Alzheimer’s, Study Suggests

Failed Verubecestat Trial May Call into Question Beta-amyloid Theory in Alzheimer’s, Study Suggests
Verubecestat (MK-8931) indeed failed to slow cognitive and functional decline in mild-to-moderate Alzheimer’s patients despite some reduction in beta-amyloid levels seen, final results of a Phase 2/3 study closed early by Merck for lack of efficacy confirmed. The researchers behind this study suggested these findings may call into question whether the amyloid hypothesis of Alzheimer’s is "correct," or whether it is relevant "once dementia is present." The findings were published in the New England Journal of Medicine, in a study titled “Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer’s Disease.” Verubecestat is an oral inhibitor of the BACE1 enzyme — the enzyme responsible for the cleavage of the amyloid precursor protein, which is the first step in the production of beta-amyloid molecules that accumulate and trigger Alzheimer’s disease. Verubecestat had been shown to reduce beta-amyloid levels in the cerebrospinal fluid of healthy people and Alzheimer’s patients by more than 75%, suggesting that it could prevent further cognitive and functional decline in patients with the disease. To evaluate the safety and effectiveness of two doses of verubecestat in patients with mild-to-moderate Alzheimer’s, Merck opened a Phase 2/3 study, called EPOCH (
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