Alzheimer's disease drug development pipeline: 2020

Abstract

Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for AD.

Methods: We reviewed ClinicalTrials.gov as of February 27, 2020, and identified all trials of pharmacologic agents currently being developed for treatment of AD as represented on this widely used U.S. Food and Drug Administration registry.

Results: There are 121 agents in clinical trials for the treatment of AD. Twenty-nine agents are in 36 Phase 3 trials, 65 agents are in 73 Phase 2 trials, and 27 agents are in 27 Phase 1 trials. Twelve agents in trials target cognitive enhancement and 12 are intended to treat neuropsychiatric and behavioral symptoms. There are 97 agents in disease modification trials. Compared to the 2019 pipeline, there is an increase in the number of disease-modifying agents targeting pathways other than amyloid or tau.

Discussion: The 2020 pipeline has innovations in clinical trials and treatment targets that provide hope for greater success in AD drug development programs. Review of clinical trials over the past 5 years show that there is progressive emphasis on non-amyloid targets, including candidate treatments for inflammation, synapse and neuronal protection, vascular factors, neurogenesis, and epigenetic interventions. There has been a marked growth in repurposed agents in the pipeline.

Keywords: Alzheimer's disease; Common Alzheimer's and Related Dementias Research Ontology (CADRO); NIH; biomarkers; clinical trials; drug development; pharmaceutical companies; repurposed drugs.

FIGURE 1

Agents in clinical trials for treatment of Alzheimer's disease in 2020 (from ClinicalTrials.gov as of February 27, 2020. 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 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. Agents underlined are new to the pipeline since 2019 (Figure by Mike de la Flor)

FIGURE 2

Mechanisms of action of agents in Phase 3 of the Alzheimer's disease drug development pipeline (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)

FIGURE 3

Mechanisms of action of agents in Phase 2 of the Alzheimer's disease drug development pipeline (ClinicalTrials.gov accessed February 27, 2020)(Figure by Mike de la Flor)

FIGURE 4

Trial sponsor for repurposed versus non‐repurposed agents in the Alzheimer's disease pipeline (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)

FIGURE 5

Location of sites for Phase 2 and Phase 3 trials in the Alzheimer's disease drug development pipeline (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)

FIGURE 6

Targets of Alzheimer's disease therapeutics by Common Alzheimer's Disease and Related Disorders Research Ontology (CADRO) category: 2016–2020 (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)

FIGURE 7

Percent of Phase 2 and 3 disease‐modifying therapy trials requiring amyloid evidence (positron emission tomography, cerebrospinal fluid or either) at entry: 2016–2020 (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)

FIGURE 8

Phase 2 and Phase 3 disease‐modifying therapy trials using Alzheimer's disease biomarkers as outcome measures: 2016–2020 (ClinicalTrials.gov accessed February 27, 2020) (Figure by Mike de la Flor)