Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease

Abstract INTRODUCTION In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item‐level data and the persistence of treatment benefit. METHODS Participants with early Alzheimer's disease (AD) were stratified by apolipoprotein E ( APOE ) ε4 status and randomized (1:1:1) to receive low‐ or high‐dose aducanumab, or placebo. Prespecified principal component analyses (PCAs) per the Statistical Analysis Plan were followed by post hoc examination of individual domains/items across all five clinical endpoints. Progression analysis assessed reduction in clinical decline. RESULTS High‐dose aducanumab demonstrated clinically meaningful slowing of progression across clinical endpoints measuring cognition, daily function, and behavioral symptoms. Delay of progression over 18 months was consistent across measures; treatment effects increased over time. DISCUSSION Across multiple analyses aducanumab slowed cognitive decline, prolonged functional independence, and attenuated behavioral symptoms in participants with early AD. These outcomes comprise the elements of a clinically meaningful response to treatment. Highlights Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms. Treatment benefits were observed across subdomains on all five clinical endpoints. Aducanumab meaningfully slowed disease progression in participants with early AD.