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TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease

Published online by Cambridge University Press:  07 July 2023

Stephen Salloway ,
Elly Lee ,
Michelle Papka ,
Andrew Pain ,
Ena Oru ,
Margaret B. Ferguson ,
Hong Wang ,
Michael Case ,
Ming Lu  and
Emily C Collins
...Show all authors
Stephen Salloway
Affiliation:
Department of Neurology and Department of Psychiatry, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America Butler Hospital, Providence, Rhode Island, United States of America
Elly Lee
Affiliation:
Irvine Clinical Research, Irvine, California, United States of America
Michelle Papka
Affiliation:
The Cognitive and Research Center of New Jersey LLC, Springfield, New Jersey, United States of America
Andrew Pain*
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Ena Oru
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Margaret B. Ferguson
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Hong Wang
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Michael Case
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Ming Lu
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Emily C Collins
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
Dawn A. Brooks
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
John Sims
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, United States of America
*
*Corresponding author.
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Abstract

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Aims

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. 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.

Methods

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

Conclusion

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.

Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.

Type
Research
Information
BJPsych Open , Volume 9 , Supplement S1: Abstracts from the RCPsych International Congress 2023, 10–13 July , July 2023 , pp. S67
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NC
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This does not need to be placed under each abstract, just each page is fine.
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

Footnotes

Abstracts were reviewed by the RCPsych Academic Faculty rather than by the standard BJPsych Open peer review process and should not be quoted as peer-reviewed by BJPsych Open in any subsequent publication.

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