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Alzheimer's disease drug development pipeline: 2018
Open accessAbstract
Introduction: Treatments for Alzheimer's disease (AD) are needed due to the growing number of individuals with preclinical, prodromal, and dementia forms of AD. Drug development for AD therapies can be examined by inspecting the drug development pipeline as represented on clinicaltrials.gov . Methods: Clinicaltrials.gov was assessed as of January 30, 2018 to determine AD therapies represented in phase I, phase II, and phase III. Results: There are 112 agents in the current AD treatment pipeline. There are 26 agents in 35 trials in phase III, 63 agents in 75 trials in phase II, and 23 agents in 25 trials in phase I. A review of the mechanisms of actions of the agents in the pipeline shows that 63% are disease‐modifying therapies, 22% are symptomatic cognitive enhancers, and 12% are symptomatic agents addressing neuropsychiatric and behavioral changes. Trials in phase III are larger and longer than phase II or phase I trials, particularly those involving disease‐modifying agents. Comparison with the 2017 pipeline shows that there are four new agents in phase III, 14 in phase II, and eight in phase I. Inspection of the use of biomarkers as revealed on clinicaltrials.gov shows that amyloid biomarkers are used as entry criterion in 14 phase III disease‐modifying agent trials and 17 disease‐modifying agent trials in phase II. Twenty‐one trials of disease‐modifying agents in phase II did not require biomarker confirmation for AD at trial entry. Discussion: The AD drug development pipeline is slightly larger in 2018 than in 2017. Trials increasingly include preclinical and prodromal populations. There is an increase in nonamyloid mechanisms of action for drugs in earlier phases of drug development. Biomarkers are increasingly used in AD drug development but are not used uniformly for AD diagnosis confirmation.
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“A number of additional pathogenic mechanisms have been described, possibly overlapping with Aβ plaques and NFT formation or induced by them, including inflammation, oxidative damage, iron deregulation, and cholesterol metabolism blood-brain barrier (BBB) dysfunction or α-synuclein toxicity.9-13”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [13]
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“Moreover, the literature review reveals that only a single cholinesterase inhibitor is in Phase II and Phase III clinical trials, for AD management [147,148].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [148]
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Metadata
- Authors
- Cummings, J., Lee, G., Ritter, A., & Zhong, K.
- Affiliations
- Cleveland Clinic (US)
- Global Alzheimer's Platform Foundation (US)
- Corresponding author
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2018-01
- Volume
- 4
- Issue
- 1
- Pages
- 195-214
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC6021548
- OpenAlex
- W2918066696
- Cited by
- 697
- References
- 48
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 39 · 2023: 22 · 2022: 55 · 2021: 138 · 2020: 177 · 2019: 170 · 2018: 42
- FWCI
- 91.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (P20GM109025)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, drug development pipeline, clinical trials, disease-modifying therapy, amyloid biomarkers, prodromal Alzheimer's disease, preclinical Alzheimer's disease, neuropsychiatric symptoms
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