Document Type
Article
Publication Date
7-9-2019
Publication Title
Alzheimer's and Dementia: Translational Research and Clinical Interventions
Publisher
Elsevier
Volume
5
First page number:
272
Last page number:
293
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
Alzheimer's disease; Drug development; Clinical trials; Biomarkers; Bayesian design; Adaptive design; Repurposed drugs
Disciplines
Pharmaceutics and Drug Design
File Format
File Size
947 KB
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Repository Citation
Cummings, J.,
Lee, G.,
Ritter, A.,
Sabbagh, M.,
Zhong, K.
(2019).
Alzheimer's Disease Drug Development Pipeline: 2019.
Alzheimer's and Dementia: Translational Research and Clinical Interventions, 5
272-293.
Elsevier.
http://dx.doi.org/10.1016/j.trci.2019.05.008