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. 2019 Jul 9:5:272-293.
doi: 10.1016/j.trci.2019.05.008. eCollection 2019.

Alzheimer's disease drug development pipeline: 2019

Jeffrey Cummings  1   2 , Garam Lee  2 , Aaron Ritter  2 , Marwan Sabbagh  2 , Kate Zhong  3
Affiliations

Alzheimer's disease drug development pipeline: 2019

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

Abstract

Introduction: Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices.

Methods: We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD.

Results: There are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase 1 trials. There is an increase in the number of agents in each phase compared with that in the 2018 pipeline. Nineteen agents in trials target cognitive enhancement, and 14 are intended to treat neuropsychiatric and behavioral symptoms. There are 96 agents in disease modification trials; of these, 38 (40%) have amyloid as the primary target or as one of several effects. Eighteen of the antiamyloid agents are small molecules, and 20 are monoclonal antibodies or biological therapies. Seven small molecules and ten biologics have tau as a primary or combination target (18%). Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials.

Discussion: Drug development continues robustly at all phases despite setbacks in several programs in the recent past. Continuing unmet needs require a commitment to growing and accelerating the pipeline.

Keywords: Adaptive design; Alzheimer's disease; Bayesian design; Biomarkers; Clinical trials; Drug development; Repurposed drugs.

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Figures

Fig. 1
Fig. 1
All compounds in AD clinical trials as of February 12, 2019 (the inner ring shows phase 3 agents; the middle ring is comprised of phase 2 agents; the outer ring presents phase 1 compounds; agents in green areas are biologics; agents in purple areas 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 class of target for the agent.). Bolded names represent agents new to that phase since 2018.
Fig. 2
Fig. 2
Mechanisms of action of agents in phase 3.
Fig. 3
Fig. 3
Mechanisms of action of agents in phase 2.
See this image and copyright information in PMC

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References

    1. Dubois B., Feldman H.H., Jacova C., Cummings J.L., Dekosky S.T., Barberger-Gateau P. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol. 2010;9:1118–1127. - PubMed
    1. Dubois B., Hampel H., Feldman H.H., Scheltens P., Aisen P., Andrieu S. Preclinical Alzheimer's disease: definition, natural history, and diagnostic criteria. Alzheimer's & dementia. J Alzheimer's Assoc. 2016;12:292–323. - PMC - PubMed
    1. Aisen P.S., Andrieu S., Sampaio C., Carrillo M., Khachaturian Z.S., Dubois B. Report of the task force on designing clinical trials in early (predementia) AD. Neurology. 2011;76:280–286. - PMC - PubMed
    1. U.S. Food and Drug Administration . 2013. Guidance for Industry Alzheimer's Disease: Developing Drugs for the Treatment of Early Stage Disease. Food and Drug Administration, Washington, D.C.
    1. U.S. Food and Drug Administration. U.S. Department of Health and Human Services . Guidance for Industry; Washington, DC: 2018. Early Alzheimer's Disease: Developing Drugs for Treatment.