Merck has announced that it will be stopping protocol 017, also known as the EPOCH study, a phase 2/3 study evaluating verubecestat, an investigational small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), in people with mild-to-moderate Alzheimer’s disease (AD). Merck is stopping the study following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during a recent interim safety analysis, and determined that there was virtually no chance of finding a positive clinical effect. The eDMC noted that safety signals observed in the study are not sufficient to warrant stopping study 017, and recommended that protocol 019, also known as APECS, which is evaluating verubecestat in people with prodromal Alzheimer’s disease, continue unchanged. Results from protocol 019 are expected in February 2019. Results from EPOCH will be analyzed and presented at an upcoming scientific meeting.
“Alzheimer’s disease is one of the most pressing and daunting medical issues of our time, with inherent, substantial challenges to developing an effective disease-modifying therapy for people with mild-to-moderate disease. Studies such as EPOCH are critical, and we are indebted to the patients in this study and their caregivers,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “While we are disappointed that a benefit was not observed in this study, our work continues with APECS, which is studying verubecestat in people with less advanced disease.”
The efficacy and safety of verubecestat was being evaluated in two pivotal Phase 3 clinical trials: Protocol 017, or EPOCH, in mild-to-moderate AD, and Protocol 019, or APECS, in prodromal AD. Patients with mild to moderate AD exhibit detectable and worsening impairment of cognitive and functional abilities. Patients with prodromal AD have objective memory problems but relatively normal functioning in activities of daily living.