Abstract
IntroductionAlzheimer'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. MethodsWe reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD. ResultsThere 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. DiscussionDrug 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.
Highlights
Drug discovery and development for Alzheimer’s disease (AD) is arduous
We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD
We describe clinical trials and experimental treatments for disease modification, cognitive enhancement, and neuropsychiatric symptoms of AD
Summary
Drug discovery and development for Alzheimer’s disease (AD) is arduous. There have been no new drugs approved since 2003, and there are no approved disease-modifying treatments (DMTs) for AD. The US Food and Drug Administration (FDA) has provided guidance for Disclosures: Dr Cummings has provided consultation to Acadia, Accera, Actinogen, Alkahest, Allergan, Alzheon, Avanir, Axsome, BiOasis Technologies, Biogen, Cognicity, Diadem, EIP Pharma, Eisai, Genentech, Green Valley, Grifols, Hisun, Idorsia, Karuna, Kyowa Kirin, Lilly, Lundbeck, Merck, Otsuka, Proclara, QR, Resverlogix, Roche, Samus, Samumed, Sunovion, Suven, Takeda, Teva, Toyama, and United Neuroscience pharmaceutical and assessment companies. Dr Sabbagh reported Royalties from Harper Collins, Stock/Equity from uMethodHealth, Brain Health Inc, Optimal Cognitive Health Company, M3 Biosciences, Versanum; Speakers Bureau from Peerview and Rockpointe, Consultant/Advisor for Allergan, Biogen, Bracket, Neurotrope, Cortexyme, Roche, Grifols, Regeneron, VTV therapeutics, Alzheon.
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