Verubecestat Pharmacokinetic and Exposure-Response Results From APECS, a Phase 3 Trial in Prodromal Alzheimer’s Disease

Authors: Stone J, Kleijn H, Jaworowicz DJ, Passarell JA, Dockendorf M, Xu M, Rasmussen C, Humphrey RL, Voss T, Egan M
Publication: Alzheimer’s & Dementia
Keywords: APECS, BACE inhibitor, exposure-response, MK-8931, pharmacokinetic, verubecestat
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

The BACE inhibitor verubecestat (MK-8931) demonstrated cognitive and functional decline relative to placebo in a 2-year Phase 3 trial of individuals with prodromal AD (APECS; NCT01953601), along with reductions in brain volume and amyloid plaque. Disease progression modeling has demonstrated a lack of dose- or exposure-dependency in the clinical cognition and function endpoints (see separate abstract). In this analysis, pharmacokinetic (PK) and safety and biomarker data from the trial were examined to characterize target engagement and biomarker exposure-response.

By, Julie A. Stone, Huub Jan Kleijn, David J. Jaworowicz, Julie Passarell, Marissa Dockendorf, Ming Xu, Christian Rasmussen, Rebecca Humphrey, Tiffini Voss, Michael F. Egan