EPOCH, which began in late 2012, sought to improve Alzheimer’s disease symptoms by slowing deposition of the beta-amyloid plaques characteristic of AD. The first step in beta-amyloid production requires a BACE enzyme. This study tested verubecestat, an inhibitor of one such BACE enzyme, in patients with mild-to-moderate Alzheimer’s disease.
An interim analysis of the study presented “virtually no chance of finding a positive clinical effect,” Merck said in a statement. The advanced disease stage of study participants provided a primary motivation to stop the trial. In late disease stages, beta-amyloid levels have largely stabilized, contributing to significant synaptic and neuronal damage. Once AD has progressed to this point, it is unlikely that slowing amyloid production will reduce symptoms. In other words, the damage has already been done.
None of this is to say, however, that verubecestat will not prove useful in the future. Verubecestat and other BACEs may be employed more effectively as preventative treatments. In fact, Merck plans to continue its APECS study, which applies the same doses of verubecestat to individuals in earlier disease stages. Other studies are currently testing the preventative role of BACEs in asymptomatic individuals, especially in those genetically predisposed to develop AD.
Paul Aisen of UC San Diego maintained hope that “very early treatment with these drugs may be quite effective.” Merck anticipates APECS study results will become available by February of 2019.
In short, prevention may slow disease progression when utilized early on. Applying a preventative treatment in later stages of Alzheimer’s Disease, by contrast, is unlikely to reverse severe symptoms.
“Alzheimer’s disease is one of the most pressing and daunting medical issues of our time,” said Dr. Roger M. Perlmutter, president of Merck research laboratories, also noting the inherent challenges in developing effective therapies for mild-to-moderate cases of AD. While EPOCH did not yield a positive result, Perlmutter maintained that such studies are critical, “and we are indebted to the patients in this study and their caregivers.”
— by Grace Ragi