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

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.

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.

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 $5,000-$9,999 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 $500-$4,999 for serving as a Consultant for Amylyx. 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 $500-$4,999 for serving as a Consultant for Ono. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bolden. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EISAI. Dr. Salloway has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acumen. Dr. Salloway has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly.
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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)	No disclosure on file
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	No disclosure on file
Emily Collins (Eli Lilly)	No disclosure on file
Dawn Brooks (Eli Lilly and Company)	No disclosure on file
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.