The fourth version of the Cleveland Clinic’s Alzheimer pipeline includes 156 clinical trials and 132 agents currently in all 3 phases of clinical trials in the US.
Aaron Ritter, MD
The Cleveland Clinic’s fourth annual Alzheimer disease (AD) drug development pipeline presents a new round of clinical trials to give clinicians a comprehensive look at current research in the US.
The investigators, led by Jeffrey Cummings, MD, ScD, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health, identified all pharmacologic Alzheimer trials currently in development from Clinicaltrials.gov. They found 132 agents currently in 156 clinical trials—28 of which are in 42 phase 3 trials; 74 in 83 phase 2 trials; and 30 in 31 phase 1 trials.
Currently in the Alzheimer disease pipeline are 19 agents in trials targeting cognitive enhancement, 14 treating neuropsychiatric and behavioral symptoms, and 96 agents in disease modification trials, of which 38 are focusing on amyloid as either the primary target or as 1 of several effects.
Of the amyloid targeting agents, 18 are small molecules, and 20 are monoclonal antibodies or biological therapies. Also in development are 7 small molecules and 10 biologics that have tau as either the primary target or as a combination target.
The team also found some new features in clinical trials, including new biomarkers and outcomes, enrollment of earlier populations, and innovative trial designs.
AD comes with very few available treatment options because most drug development programs are taxing and unsuccessful, which is evident in the fact that there has not been a new drug approved to treat the disease since 2003.
However, Aaron Ritter, MD, director of clinical trials at the Lou Ruvo Center, explained in an interview with MD Magazine® how drug development pipelines identify the evolution of drug development and lead to optimized development practices.
“I think the thing that we are seeing in the pipeline that we are really encouraged by is that there are different targets for medicines,” Ritter said. “At this point we know that certain proteins are associated with Alzheimer’s disease, but we still don’t know what’s really causing and driving the disease to progress, and why some people get it and some people don’t.”
Ritter explained the main difference between the first iteration of the pipeline and the current version is that the trials have become more advanced, diversified, and sophisticated.
With an aging population, investigators are expected to continue to push for a better understanding of AD.
“The population is graying, the fastest growing population is going to be people over the age of 90 in the next 20 or 30 years,” Ritter said. “The question is, are we 100 feet away or 10 feet away from solving the problem?”
However, as research in this field continues to grow, Ritter said there is a critical need for both people with the disease and those at risk of developing the disease to participate in clinical trials, estimating that 50,000 people in the US are needed to test all the therapies currently in the pipeline.
Currently, the US Food and Drug Administration (FDA) has guidelines for clinical trials for AD dementia and predementia AD, including using a single primary outcome in trials of prodromal AD, the role of biomarkers in staging preclinical and prodromal AD, and using Bayesian statistics and adaptive clinical trial designs.
The National Institute of Aging has also released new research framework based on amyloid, tau, and neurodegeneration biomarkers to allow for more precise classification of stages of AD, particularly predementia stages.
Ritter said an issue stifling research is that there isn’t a lot of openness in regard to what the major research institutions are working on.
“One of the big issues in any type of research is it is often siloed into different institutions, it is just the way that research in this country has kind of developed,” he said. “The idea of the pipeline is to just give a broad overview of what everyone is doing and hopefully spurring some collaborations.”
The study, “Alzheimer's disease drug development pipeline: 2019,” was published online in Alzheimer’s & Dementia: Translational Research & Clinical Interventions.