Abstract Details

Title Subgroup Analyses of the Amyloid PET Substudies From EMERGE and ENGAGE, Phase 3 Clinical Trials Evaluating Aducanumab in Patients With Early Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 012

Objective To examine the effects of aducanumab treatment on brain amyloid beta (Aβ) plaque levels in prespecified baseline and disease characteristics subgroups of patients from the Phase 3 EMERGE and ENGAGE trials.

Background Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ. EMERGE and ENGAGE evaluated the efficacy and safety of aducanumab in participants with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or mild AD dementia and confirmed amyloid pathology. In these studies, dose- and time-dependent reductions in amyloid positron emission tomography (PET) composite standard uptake value ratio (SUVR) were observed at Week 78 in the amyloid PET biomarker substudies.

Design/Methods Participants were randomized (1:1:1) to receive high-dose aducanumab, low-dose aducanumab, or placebo via intravenous injection monthly for 18 months. Longitudinal amyloid PET imaging (¹⁸F-florbetapir) was performed in a subset of patients (488 in EMERGE; 585 in ENGAGE) at screening, Week 26, and Week 78.

Subgroup analysis of amyloid PET SUVR for 6 prespecified factors including age (≤64, 65-74, or ≥75 years), sex (male or female), apolipoprotein E ε4 status (carrier or noncarrier), baseline clinical stage (MCI due to AD or mild AD dementia), baseline Mini-Mental State Exam (≤26 or ≥27) and use of AD symptomatic medications at baseline (yes or no) for a total of 13 subgroups was conducted for each study.

Results An advantage of high- and low-dose aducanumab over placebo was observed in the 13 subgroups, with time- and dose-dependent Aβ reduction observed in each subgroup. These results were consistent with the overall results of the amyloid PET biomarker substudies in which aducanumab treatment was associated with robust dose-dependent reduction in brain Aβ levels.

Conclusions Amyloid PET SUVR subgroup analysis revealed a consistent dose- and time-dependent advantage of high- and low-dose aducanumab over placebo in the prespecified subgroups.

Authors/Disclosures
Tianle Chen, PhD PRESENTER	Dr. Chen has received personal compensation for serving as an employee of Biogen.
Michael Stalder (SiteRX)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Carmen Castrillo-Viguera	Dr. Castrillo-Viguera has received personal compensation for serving as an employee of Biogen. Dr. Castrillo-Viguera has received stock or an ownership interest from Biogen.
Ping He, MD, PhD	Dr. He has received personal compensation for serving as an employee of Biogen.
Samantha Budd Haeberlein	Samantha Budd Haeberlein has received personal compensation for serving as an employee of Biogen. An immediate family member of Samantha Budd Haeberlein has received personal compensation for serving as an employee of Alkermes. Samantha Budd Haeberlein has received stock or an ownership interest from Biogen.

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