Verubecestat

Analyst Outlook

Verubecestat’s (Merck & Co) Phase Ib studies revealed highly impressive results in its capability to

almost abolish cerebrospinal fluid (CSF) amyloid-beta fragments. The clinical implications of

verubecestat’s biological efficacy will be brought to light in two large Phase III studies evaluating its

efficacy and safety in early and mild to moderate Alzheimer’s disease patients. Until the release of

Phase III results, relatively little is known about verubecestat apart from its impressive biological

effect and short-studied safety profile. While currently in a leading position, verubecestat is to face

fierce competition from other beta-site amyloid precursor protein cleaving enzyme (BACE) inhibitors

as they transition to Phase III development. This will likely prompt Merck to hasten verubecestat’s

clinical development as the race to obtain first-to-market status intensifies.

Drug Overview

Verubecestat is an inhibitor of the BACE1. BACE1 is one of two enzymes that cleaves amyloid-beta

precursor protein, giving rise to various amyloid-beta fragments. By inhibiting the activity of BACE1,

verubecestat reduces amyloid production and thus reduces amyloid plaque deposition in the brain, a

key feature of Alzheimer’s disease. Verubecestat is currently in Phase III development for the

treatment of prodromal and mild to moderate Alzheimer’s disease (Medtrack, 2015; Merck & Co,

2015).