Abstract Details

Title TRAILBLAZER-ALZ 4: Topline study results directly comparing donanemab to aducanumab on amyloid lowering in early, symptomatic Alzheimer’s disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S26 - Experimental Therapeutics in Dementia (2:36 PM-2:48 PM)

Poster/Presentation
Number 009

Objective To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer’s disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study.

Background The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD.

Design/Methods Participants (n=148) were randomized 1:1 to receive donanemab (700mg IV Q4W [first 3 doses], then 1400mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1mg/kg IV Q4W [first 2 doses], 3mg/kg IV Q4W [next 2 doses], 6mg/kg IV Q4W [next 2 doses] and 10mg/kg IV Q4W [subsequent doses]).

Results

Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N=71], aducanumab [N=69]). Twenty seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau.

Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p<0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p=0.008).

Percent change in brain amyloid levels were -65.2%±3.9% (baseline: 98.29±27.83 CL) and -17.0%±4.0% (baseline: 102.40±35.49 CL) in donanemab and aducanumab arms, respectively (p<0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were -63.9%±7.4% (baseline: 104.97±25.68 CL) and -25.4%±7.8% (baseline: 102.23±28.13 CL) in donanemab and aducanumab arms, respectively (p≤0.001).

62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm.

Conclusions This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.

Authors/Disclosures
Stephen P. Salloway, MD, MS (Brown Medical School) PRESENTER	Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EISAI. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lilly. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NovoNordisk. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Prothena. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Salloway has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurophet. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kisbee. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CognitionRX. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Icometrix. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck.
	No disclosure on file
	No disclosure on file
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Margaret Ferguson	Margaret Ferguson has received personal compensation for serving as an employee of Eli Lilly. Margaret Ferguson has stock in Eli Lilly.
Hong Wang (Eli Lilly and company)	Hong Wang has received personal compensation for serving as an employee of Eli Lilly And Company.
Michael G. Case, MS (Eli Lilly and Company)	Mr. Case has received personal compensation for serving as an employee of Eli Lilly and Company. Mr. Case has received stock or an ownership interest from Eli Lilly and Company.
Ming Lu	Ming Lu has received personal compensation for serving as an employee of Eli Lilly and Company. Ming Lu has stock in Eli Lilly and Company.
Emily Collins (Eli Lilly)	Emily Collins has received personal compensation for serving as an employee of Eli Lilly. Emily Collins has stock in Eli Lilly.
Dawn Brooks (Eli Lilly and Company)	Dawn Brooks has received personal compensation for serving as an employee of Eli Lilly and Company. Dawn Brooks has stock in Eli Lilly and Company.
John R. Sims, MD (Eli Lilly)	Dr. Sims has received personal compensation for serving as an employee of Eli Lilly and Company. Dr. Sims has stock in Eli Lilly and Company.

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