Comprehensive analysis reiterates drug development remains direly slow, but new trends include emphasis on disease-modifying therapies and an increase in the use of biomarkers to support diagnosis
Cleveland Clinic’s third annual analysis of Alzheimer’s disease drug development reveals that drug development continues to be disappointingly slow. Researchers, however, are learning more about evolving targets in the pipeline, including a movement toward disease prevention and an emphasis in disease-modifying therapies.
The paper, Alzheimer’s disease drug development: pipeline 2018, is based on the federal website ClinicalTrials.Gov and appears as a feature article in the journal Alzheimer’s & Dementia: Translational Research & Clinical Trials Interventions (TRCI).
While the Alzheimer’s drug development pipeline is slightly larger in 2018 than 2017, researchers note that a disease-modifying therapy that will prevent or delay the onset or slow progression of the disease is urgently needed. Even a modest, one-year delay in onset by 2020 would result in there being 9.2 million fewer cases of Alzheimer’s by 2050. Of the 112 agents in the pipeline, 63 percent are disease-modifying therapies. Moreover, there is a shift to treat those with milder forms of Alzheimer’s as there are more trials in preclinical populations, including cognitively normal individuals at high risk for developing the disease (due to their genetic profile or having evidence of amyloid build up from either brain scans or cerebrospinal fluid testing).
“Cleveland Clinic continues to be a leader in assessing the evolution of new therapies for Alzheimer’s and we believe it’s crucial to drive conversation about our annual findings in effort to foster collaboration and bring public awareness to the need for acceleration of drug development,” said Aaron Ritter, M.D., director of the clinical trials program of Cleveland Clinic Lou Ruvo Center for Brain Health. “Our annual pipeline paper clearly illustrates that there just aren’t enough drugs in the Alzheimer’s disease development pipeline. We can increase our chances of finding life-changing treatments for Alzheimer’s disease by testing more drugs and doing it quickly and efficiently.”
Using a search of ClinicalTrials.Gov, Dr. Ritter, along with fellow authors Jeffrey Cummings, M.D., ScD, director emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health, Kate Zhong, M.D., Chief Strategy Officer of Global Alzheimer’s Platform and Garam Lee, Pharm.D., clinical research pharmacist at Cleveland Clinic Lou Ruvo Center for Brain Health, examined all clinical trials from 2017 to 2018 to reveal the need for greater use of biomarkers, and that while there is a shift in efforts toward preventative measures, the few number of agents targeting moderate to advanced stages of Alzheimer’s and the small number of therapies entering Phase 1 is concerning. In addition, researchers found that infused antibodies are a major type of evolving therapy that bode potentially exciting results.
For example, the recent results from aducanumab and BAN2401 trials are particularly encouraging as the antibody protein is thought to decrease the amyloid plaques and possibly slow neurodegeneration and reduce disease progression.
Furthermore, immediate challenges of drug development include the lack of surrogate biomarkers. Biomarkers are not only important for the development of disease-modifying therapies, but also symptomatic drugs and are currently used to improve diagnostic accuracy. However, review of the pipeline shows that a surprisingly low percentage of disease-modifying therapy trials requires diagnostic biomarkers for entry or secondary outcomes, concluding the development and use of biomarkers for Alzheimer’s clinical trials remains an unmet goal.
Though improvements are needed, proactive steps toward clinical trial efficiency are currently underway, including the widespread use of online registries to help recruit qualified trial participants. Researchers suggest that optimizing the use of registries as well as more rapid clinical trial start up, pre-certified raters and use of a single review board can help accelerate clinical trial execution and development.
For additional information about Cleveland Clinic Lou Ruvo Center for Brain Health, visit ClevelandClinic.org/BrainHealth. For additional information about Cleveland Clinic Center for Neurological Restoration, visit ClevelandClinic.org/Departments/Neurological/Depts/Neurological-Restoration.