Alzheimer’s drug candidate trial data disclosed | Chemical & Engineering News
Volume 94 Issue 44 | p. 12 | Concentrates
Issue Date: November 7, 2016

Alzheimer’s drug candidate trial data disclosed

BACE1 inhibitor verubecestat shows favorable side effect profile
Department: Science & Technology
News Channels: Biological SCENE
Keywords: drug discovery, verubecestat, Alzheimer’s disease, inhibitor, BACE1

In an early Phase I study, an Alzheimer’s drug candidate showed reduced side effects compared with similar drugs that have failed clinical trials. The agents inhibit BACE1, an enzyme whose activity leads to β-amyloid peptide (Aβ) production. The idea is that inhibiting Aβ formation to reduce growth of Aβ-based plaques in the brains of Alzheimer’s patients may be therapeutic, although it isn’t yet clear how early in the disease process such an intervention would need to be employed to be effective. Several BACE1 inhibitors were withdrawn from trials because of off-target side effects such as liver toxicity. The BACE1 inhibitor verubecestat (MK-8931), currently being evaluated in two Phase III trials scheduled for completion in 2017 and 2019, seems to be more benign. Matthew E. Kennedy, Andrew W. Stamford, Eric M. Parker, Mark S. Forman, and coworkers at Merck report that in Phase I studies it showed relatively mild side effects, similar to those of placebos (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aad9704). Four other BACE1 inhibitors are in clinical trials, but how their efficacy and safety compare with verubecestat’s isn’t yet clear. Riqiang Yan of Cleveland Clinic Foundation, a codiscoverer of BACE1, comments that verubecestat could offer hope to Alzheimer’s patients if its side-effect profile remains favorable when administered long-term.

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