Abstract Details

Title Item-Level Analysis of Clinical Measures in Patients With Early Symptomatic Alzheimer’s Disease Following Treatment With High-Dose Aducanumab in the Phase 3 EMERGE Study

Topic Aging, Dementia, and Behavioral Neurology

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

Poster/Presentation
Number 015

Objective

To examine the change from baseline item-level scores in primary, secondary, and tertiary clinical endpoints that assess Alzheimer’s disease (AD) in participants in EMERGE (NCT02484547).

Background EMERGE, one of 2 Phase 3 trials evaluating aducanumab in patients with early AD, demonstrated a statistically significant drug-placebo difference in prespecified primary and secondary clinical endpoints.

Design/Methods EMERGE (N=1643) included participants aged 50-85 years who had mild cognitive impairment (MCI) due to AD or mild AD dementia, with confirmed amyloid pathology. Participants were randomized to receive high- or low-dose aducanumab or placebo. The primary endpoint was change from baseline in Clinical Dementia Rating–Sum of Boxes (CDR-SB) score at Week 78; secondary outcome measures included Mini-Mental State Examination, AD Assessment Scale–Cognitive Subscale 13 items (ADAS-Cog13), and AD Cooperative Study–Activities of Daily Living (ADCS-ADL)-MCI scores. Neuropsychiatric Inventory 10-item (NPI-10) score was a tertiary outcome. Item-level analyses using a mixed model for repeated measures were conducted on these endpoints in the intent-to-treat population. Multiplicity adjustment was not considered, as the analyses were primarily descriptive.

Results Aducanumab treatment effects were observed across all CDR domains. Slowing of decline in ADAS-Cog13 items sensitive to change in early AD (e.g., orientation, word recall, word recognition, and number cancellation) and preservation of daily function across the ADCS-ADL-MCI items were observed. Aducanumab treatment was associated with attenuation of AD-related behavioral and psychiatric symptoms, as measured by NPI-10, and an accompanying decrease in caregiver distress.

Conclusions

Aducanumab treatment effects, observed across a broad array of cognitive, functional, and neuropsychiatric outcome measures, are clinically relevant. Item-level analyses demonstrated consistency across cognitive, functional, and behavioral domains sensitive to impairments that are detectable even in early AD. These measures reflect the perspectives of patients, caregivers, and clinicians, thereby supporting the importance and meaningfulness of an aducanumab treatment effect in early AD.

Authors/Disclosures
Sharon Cohen, MD PRESENTER	Dr. Cohen has nothing to disclose.
Ping He, MD, PhD	Dr. He has received personal compensation for serving as an employee of Biogen.
Mihaela Levitchi	Mihaela Levitchi has received personal compensation for serving as an employee of Biogen. Mihaela Levitchi has received stock or an ownership interest from Biogen.
	No disclosure on file
	No disclosure on file
Menglan Pang	Menglan Pang has received personal compensation for serving as an employee of Biogen. Menglan Pang has received stock or an ownership interest from Biogen.
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.
	No disclosure on file
	No disclosure on file
Anton P. Porsteinsson, MD (AD-CARE - University of Rochester School of Medicine)	Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ONO Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for WebMD. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Porsteinsson has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Xenon Pharmaceuticals. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Porsteinsson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cognitive Research Corporation. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Athira. Dr. Porsteinsson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Porsteinsson has received research support from Alector. The institution of Dr. Porsteinsson has received research support from Eisai. The institution of Dr. Porsteinsson has received research support from Eli Lilly. The institution of Dr. Porsteinsson has received research support from Athira. The institution of Dr. Porsteinsson has received research support from Genentech/Roche. The institution of Dr. Porsteinsson has received research support from Cassava. The institution of Dr. Porsteinsson has received research support from Vaccinex.
Jeffrey L. Cummings, MD, FAAN	Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol-Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. Dr. Cummings has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia, Biogen, Genentech, Grifols, Janssen, Karuna, Otsuka, reMYND, Roche, Signant Health. Dr. Cummings has stock in Artery, Vaxxinity, Behrens, Alzheon, MedAvante-Prophase, and Acumen. Dr. Cummings has received research support from NIH. Dr. Cummings has received research support from NIGMS. Dr. Cummings has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
	No disclosure on file
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.

��ɫ��

��ɫ��