Cleveland Clinic Analysis Finds that Drug Development in Alzheimer’s Still Inadequate

However, new trends include emphasis on disease-modifying therapies and an increased use of biomarkers

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.

About Cleveland Clinic Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 52,000 employees are more than 3,600 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic’s health system includes a 165-acre main campus near downtown Cleveland, 11 regional hospitals, more than 150 northern Ohio outpatient locations – including 18 full-service family health centers and three health and wellness centers – and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2017, there were 7.6 million outpatient visits, 229,000 hospital admissions and 207,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.

About Cleveland Clinic Lou Ruvo Center for Brain Health Cleveland Clinic Lou Ruvo Center for Brain Health provides expert diagnosis and treatment for individuals and families living with Alzheimer’s, Parkinson’s and Huntington’s diseases; multiple sclerosis; frontotemporal dementia and related disorders; and multiple system atrophy. The center offers a continuum of care with no-cost opportunities for the community to participate in education and research, including disease prevention studies and clinical trials of promising new medications. An integrated entity, Keep Memory Alive, raises funds exclusively in support of the Lou Ruvo Center for Brain Health in Las Vegas, Nevada. For more information, visit http://www.clevelandclinic.org/brainhealth and http://www.keepmemoryalive.org.

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