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Review
. 2023 Oct 2;30(1):83.
doi: 10.1186/s12929-023-00976-6.

Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update

Li-Kai Huang #  1   2   3 , Yi-Chun Kuan #  2   3   4   5 , Ho-Wei Lin  6 , Chaur-Jong Hu  7   8   9   10
Affiliations
Review

Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update

Li-Kai Huang et al. J Biomed Sci. .

Abstract

Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation of amyloid and tau, neuro-inflammation, and neuronal injury. Clinical trials focusing on new drugs for AD were documented in 2020, but subsequent developments have emerged since then. Notably, the US-FDA has approved Aducanumab and Lecanemab, both antibodies targeting amyloid, marking the end of a nearly two-decade period without new AD drugs. In this comprehensive report, we review all trials listed in clinicaltrials.gov, elucidating their underlying mechanisms and study designs. Ongoing clinical trials are investigating numerous promising new drugs for AD. The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. These trends underscore the significance of conducting fundamental research on pathophysiology, prevention, and intervention prior to the occurrence of brain damage caused by AD.

Keywords: Alzheimer disease; Anti-amyloid; Anti-tau; Clinical trials; Cognitive enhancement; Neuroinflammation; Neuroprotection.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
According to the amyloid hypothesis, the pathophysiology and clinical course of Alzheimer's disease progress as follows: amyloid accumulation, neuroinflammation, tau accumulation, brain metabolism dysfunction, brain atrophy, cognitive decline (from mild cognitive impairment to dementia), and the development of dementia symptoms. Novel drugs should target at least one of these events. AD Alzheimer's disease, aMCI amnestic mild cognitive impairment, BPSD behavioral psychological symptoms of dementia
Fig 2.
Fig 2.
Trends in Phase 3 trials, 2020–2023, categorized according to event-related themes in ClinicalTrials.gov. Left: Number of Phase 3 trials. Right: Percentage of Phase 3 trials. A anti-amyloid therapy, B anti-tau therapy, C neuroprotection, D anti-neuroinflammation, E cognitive enhancer, F relief of behavioral psychological symptoms of dementia, G others, U undisclosed
Fig. 3
Fig. 3
Trends in Phase 1 and 2 trials, 2020–2023, categorized according to event-related themes in ClinicalTrials.gov. Left: Number of Phase 2 trials. Right: Number of Phase 1 trials; A anti-amyloid therapy, B anti-tau therapy, C neuroprotection, D anti-neuroinflammation, E cognitive enhancer, F relief of behavioral psychological symptoms of dementia, G others, U undisclosed
See this image and copyright information in PMC

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