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Review
. 2023 May 25;9(2):e12385.
doi: 10.1002/trc2.12385. eCollection 2023 Apr-Jun.

Alzheimer's disease drug development pipeline: 2023

Jeffrey Cummings  1   2 , Yadi Zhou  3 , Garam Lee  4 , Kate Zhong  1   2 , Jorge Fonseca  5 , Feixiong Cheng  3   5   6
Affiliations
Review

Alzheimer's disease drug development pipeline: 2023

Jeffrey Cummings et al. Alzheimers Dement (N Y). .

Erratum in

Abstract

Introduction: Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed.

Methods: We searched ClinicalTrials.gov for all current Phase 1, 2 and 3 clinical trials for AD and mild cognitive impairment (MCI) attributed to AD. We created an automated computational database platform to search, archive, organize, and analyze the derived data. The Common Alzheimer's Disease Research Ontology (CADRO) was used to identify treatment targets and drug mechanisms.

Results: On the index date of January 1, 2023, there were 187 trials assessing 141 unique treatments for AD. Phase 3 included 36 agents in 55 trials; 87 agents were in 99 Phase 2 trials; and Phase 1 had 31 agents in 33 trials. Disease-modifying therapies were the most common drugs comprising 79% of drugs in trials. Twenty-eight percent of candidate therapies are repurposed agents. Populating all current Phase 1, 2, and 3 trials will require 57,465 participants.

Discussion: The AD drug development pipeline is advancing agents directed at a variety of target processes.

Highlights: There are currently 187 trials assessing 141 drugs for the treatment of Alzheimer's disease (AD).Drugs in the AD pipeline address a variety of pathological processes.More than 57,000 participants will be required to populate all currently registered trials.

Keywords: Alzheimer's disease; Common Alzheimer's Disease Research Ontology (CADRO); amyloid; biomarkers; clinical trials; drug development; inflammation; pharmaceutical companies; repurposed drugs; synaptic function; tau.

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Conflict of interest statement

J.C. has provided consultation to Acadia, Alkahest, AlphaCognition, AriBio, Avanir, Axsome, Behren Therapeutics, Biogen, Biohaven, Cassava, Cerecin, Cortexyme, Diadem, EIP Pharma, Eisai, GemVax, Genentech, Green Valley, Grifols, Janssen, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Ono, Otsuka, PRODEO, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, United Neuroscience, and Unlearn AI pharmaceutical, assessment, and investment companies. J.C. is supported by NIGMS grant P20GM109025. NINDS grant U01NS093334. NIA grant R01AG053798. NIA grant P20AG068053. NIA grant R35AG71476. and the Alzheimer's Disease Drug Discovery Foundation (ADDF). J.C. owns the copyright of the Neuropsychiatric Inventory. G.L. is a full‐time employee of Biogen. K.Z. is the CEO of CNS Innovations. Y.Z. and J.F. declare no competing interests. F.C. is supported by the NIA under Award Numbers U01AG073323, R01AG076448, R01AG082211, R01AG066707, 3R01AG066707‐01S1, 3R01AG066707‐02S1, R56AG074001, and R35AG71476. F.C. declares no other competing interests. Author disclosures are available in thesupporting information.

Figures

FIGURE 1
FIGURE 1
Agents in clinical trials for treatment of Alzheimer's disease in 2023 (from ClinicalTrials.gov as of the index date of January 1, 2023). The inner ring shows Phase 3 agents; the middle ring comprises Phase 2 agents; the outer ring presents Phase 1 therapies; agents in green areas are biologics; agents in purple are disease‐modifying small molecules; agents in orange areas are symptomatic agents addressing cognitive enhancement or behavioral and neuropsychiatric symptoms; the shape of the icon shows the population of the trial; the icon color shows the CADRO‐based class of the agent (“Other” category includes CADRO classes that have three or fewer agents in trials). CADRO, Common Alzheimer's Disease Research Ontology; Tx, treatment. (Figure © J Cummings; M de la Flor, PhD, Illustrator).
FIGURE 2
FIGURE 2
Mechanisms of action of agents in Phase 3 (as classified using the CADRO approach). CADRO, Common Alzheimer's Disease Research Ontology; DMT, disease‐modifying therapy. (Figure © J Cummings; M de la Flor, PhD, Illustrator).
FIGURE 3
FIGURE 3
Mechanisms of action of agents in Phase 2. APOE, apolipoprotein E; DMT, disease‐modifying therapy. (Figure © J Cummings; M de la Flor, PhD, Illustrator).
FIGURE 4
FIGURE 4
Mechanisms of action of all agents in all phases of clinical trials grouped according to the Common Alzheimer's Disease Research Ontology (CADRO). APOE, apolipoproein E. (Figure © J Cummings; M de la Flor, PhD, Illustrator).
See this image and copyright information in PMC

References

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