Verubecestat (MK-8931) was an experimental drug for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. It is an inhibitor of

beta-secretase 1 Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is enc ...

(BACE1), which, after initial promise proved disappointing. In April 2012 phase I clinical results were announced. Phase 1b results have also been reported. it was in two phase 2/3 clinical trials that have progressed to phase 3. EPOCH, was to complete data collection for the primary outcome measure by June 2017. However, in February 2017 Merck halted its late-stage trial of verubecestat for mild to moderate Alzheimer's disease after it was reported as having "virtually no chance of finding a positive clinical effect" according to an independent panel of experts. The results of Merck's trial of verubecestat on patients with

prodromal In medicine, a prodrome is an early sign or symptom (or set of signs and symptoms) that often indicates the onset of a disease before more diagnostically specific signs and symptoms develop. It is derived from the Greek word ''prodromos'', meaning ...

(early stage) Alzheimer's were expected in February 2019. However, the trial was terminated in February 2018, after a data monitoring committee concluded it was unlikely that the drug would show a positive benefit/risk ratio. The final conclusion was that "verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer’s disease and was associated with treatment-related adverse events". Verubecestat was projected to be a breakthrough medicine for dementia related illness, however it is still unknown why the medicine was not effective in humans.

References

{{Anti-dementia drugs Fluoroarenes Carboxamides Enzyme inhibitors Alzheimer's disease research