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Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials

Authors
  • Tian Hui Kwan, Angela
  • Arfaie, Saman
  • Therriault, Joseph
  • Rosa-Neto, Pedro
  • Gauthier, Serge
Type
Published Article
Journal
Dementia and Geriatric Cognitive Disorders
Publisher
S. Karger AG
Publication Date
Dec 15, 2020
Volume
49
Issue
4
Pages
334–348
Identifiers
DOI: 10.1159/000511506
PMID: 33321511
Source
Karger
Keywords
License
Green
External links

Abstract

Background: Alzheimer disease (AD) is a chronic neurodegenerative disorder with complex pathophysiology that affects over 50 million people worldwide. Most drug therapies, to date, have focused on targeting the amyloid-beta (Aβ) pathway, but clinical outcomes of anti-Aβ antibodies have been unsuccessful and unable to meet their primary endpoints. Similar trends have also been observed in treatments that target the tau pathway. Summary: This paper reviews recent anti-Aβ passive monotherapies, since Bapineuzumab, that have progressed to phase 3 clinical trials. Specifically, we discuss the 4 clinical trial programs of Solanezumab (targets Aβ monomers), Aducanumab (targets Aβ oligomers and plaques), Crenezumab (targets Aβ oligomers), and Gantenerumab (targets Aβ fibrils) which are all exogenous monoclonal antibodies. We conclude with potential reasons for why they have not met their primary endpoints and discuss lessons learnt from these trials. Key Message: Future disease-modifying trials (DMTs) for AD should be conducted in asymptomatic, Aβ-positive individuals. Moreover, potential additive and/or synergistic benefits focusing on anti-Aβ and anti-tau drug combinations merit further investigation.

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