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The Alzheimer's disease drug development landscape
Pieter van Bokhoven1, Arno de Wilde2, Lisa Vermunt3,4
1Industry Alliance Office, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, The Netherlands. p.vanbokhoven@amsterdamumc.nl.
Alzheimer'S Research & Therapy
|November 12, 2021
Summary
Alzheimer's disease drug development is diversifying, with preclinical research exploring genetic risk factors like ApoE. However, amyloid-beta therapies remain dominant in both preclinical and clinical pipelines.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, characterized by amyloid-beta plaques, tau pathology, and neurodegeneration.
- Recent advancements include a shift towards biomarker-based diagnosis and identification of numerous genetic risk factors for sporadic AD.
- Despite progress, drug development for AD has faced significant challenges over the past two decades.
Purpose of the Study:
- To provide a comprehensive overview of the Alzheimer's disease drug development landscape.
- To compare preclinical and clinical drug development pipelines, analyzing trends in target classes and therapeutic modalities.
- To identify differences and similarities between early-stage and late-stage AD drug development.
Main Methods:
- Analysis of proprietary and public databases, company websites, and clinical trial registries for AD drugs.
- Categorization of drugs based on target class and therapeutic modality.
- Comparison of drug development trends in preclinical versus clinical stages.
Main Results:
- Preclinical pipelines show a higher proportion of interventions targeting genetic risk factors (e.g., ApoE, lipids, lysosomal targets, proteostasis) compared to clinical pipelines.
- Novel therapeutic modalities (gene therapy, enzyme treatments) are more frequently developed for traditional targets (amyloid-beta, tau).
- Amyloid-beta targeting therapies remain prevalent (19.2% preclinical, 10.7% clinical), indicating limited diversification away from this target. Inflammation is the second most targeted class in both stages.
Conclusions:
- The Alzheimer's disease drug development pipeline is diversifying in targets and modalities, yet amyloid-beta therapies persist.
- Novel companion diagnostics are crucial for patient stratification and efficacy assessment, particularly for targets related to genetic risk factors.
- Further research into genetic risk factors and development of targeted therapies are essential for advancing AD treatment.
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