Merck has announced that it will stop its phase 2/3 EPOCH trial of verubecestat, an investigational small-molecule inhibitor of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), in subjects with mild-to-moderate Alzheimer’s disease (AD). Merck is terminating the study after an external data-monitoring committee, which assessed overall benefit/risk during an interim safety analysis, determined that there was “virtually no chance of finding a positive clinical effect.”
The committee recommended, however, that another study, APECS, which is evaluating verubecestat in subjects with prodromal AD, continue unchanged. Results from that study are expected in February 2019.
The randomized, placebo-controlled, parallel-group, double-blind EPOCH trial evaluated the efficacy and safety of two oral doses of verubecestat (12 mg and 40 mg) administered once daily compared with placebo in subjects with mild-to-moderate AD who were receiving standard-of-care treatment. The coprimary efficacy endpoints were the change from baseline in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale score and the change from baseline in the Alzheimer's Disease Cooperative Study–Activities of Daily Living score after 78 weeks of treatment.
Some researchers believe that BACE inhibitors should be used in the earliest stages of AD. By the time amyloid plaques build up in the brains of AD patients, it may be too late for those drugs to be effective.
Meanwhile, Boston-based Biogen is counting on its own amyloid-targeting drug, aducanumab. Last year, the company announced positive results from a phase 1b study. Late-stage data will not be available for a few years.