Abstract Details

Title Reductions in Biomarkers of Alzheimer’s Disease Pathophysiology Following Treatment With Aducanumab Were Associated With Slowing in Clinical Decline

Topic Aging, Dementia, and Behavioral Neurology

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

Poster/Presentation
Number 013

Objective To examine whether aducanumab-induced reduction in brain amyloid beta (Aβ) plaques and downstream biomarkers of Alzheimer’s disease (AD) are associated with slowed clinical decline.

Background AD is characterized by accumulation of Aβ and tau in the brain. Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ. In clinical studies, aducanumab treatment resulted in dose- and time-dependent reduction in Aβ levels, accompanied by slowed clinical decline.

Design/Methods

Participants in the Phase 1b PRIME (NCT01677572) study were randomized to receive aducanumab or placebo every 4 weeks (q4w). Effects of aducanumab on amyloid positron emission tomography (PET) composite standard uptake value ratio and exploratory clinical endpoints were evaluated at Week 54.

Participants in the Phase 3 EMERGE (NCT02484547) and ENGAGE (NCT02477800) studies were randomized (1:1:1) to receive high-dose aducanumab, low-dose aducanumab, or placebo q4w. At Week 78, the effects of aducanumab on clinical endpoints were assessed; the effects on AD biomarkers were assessed in amyloid PET and cerebrospinal fluid (p-tau and t-tau) substudies.

Participant-level correlations between change from baseline in clinical endpoints and change from baseline in AD biomarker endpoints at Week 78 were examined in the EMERGE and ENGAGE substudies. The same analysis was conducted in PRIME. Group-level correlation between treatment effect on Aβ levels and clinical decline was conducted across all 3 studies.

Results Findings from EMERGE suggest that aducanumab-induced reductions in AD biomarker levels are associated with slowing cognitive decline. Analyses from PRIME are supportive of these findings. In ENGAGE, correlations were less apparent. However, group-level analyses based on data from PRIME, EMERGE, and ENGAGE demonstrated a correlation between aducanumab treatment effect on amyloid pathology and clinical measures.

Conclusions The correlation analyses between biomarkers and clinical measures provide evidence that aducanumab-induced reduction in biomarkers of AD disease pathophysiology is associated with slowed clinical decline.

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
	No disclosure on file
Ping He, MD, PhD	Dr. He has received personal compensation for serving as an employee of 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.
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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