Alzheimer's Disease Drug Fails in Clinical Trial

Merck recently announced that a clinical study of verubecestat in patients with mild-to-moderate Alzheimer’s disease will be stopped due to a lack of observed efficacy.

A review of the phase 2/3 EPOCH study by an external data monitoring committee indicated that there was “virtually no chance of finding a positive clinical effect” of verubecestat in patients with Alzheimer’s disease, Merck reported in a press release.

In the EPOCH clinical trial, patients with mild-to-moderate Alzheimer’s disease were randomized to receive either 12-mg or 40-mg of verubecestat or placebo once per day. The primary efficacy endpoints included the change from baseline in Alzheimer’s Disease Assessment Scale Cognitive Subscale score, and change from baseline in Alzheimer’s Disease Cooperative Study — Activities of Daily Living score after 78 weeks, according to the press release.

In light of early cessation, the investigators will analyze the EPOCH study results, and present them at an upcoming conference.

However, despite the drug failing to show efficacy in the EPOCH trial, the data committee said that the safety of the drug alone did not warrant an early stop to the study. Therefore, Merck plans to continue another clinical trial evaluating verubecestat in patients with early stages of the disease.

In the APECS clinical trial, researchers are evaluating patients with prodromal Alzheimer’s disease who have memory problems, but have normal day-to-day function. While patients were randomized to receive placebo, or 12-mg or 40-mg of verubecestat once per day, the EPOCH and APECS clinical trials vary in the symptoms experienced by the patients.

The primary efficacy outcome of this phase 3 clinical trial is the change from baseline in the Clinical Dementia Rating Scale-Sum of Boxes after 104 weeks of treatment. The study just reached full enrollment this month, and Merck plans to continue the trial unchanged until February 2019.

If verubecestat shows efficacy in this group of patients, individuals with the initial stages of Alzheimer’s disease may be able to stall disease progression before the symptoms become unmanageable.

“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 Roger M. Perlmutter, MD, PhD, 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.”