EXPERTS ADVISORY

An FDA advisory committee recommended this week that the Food and Drug Administration make donanemab, an anti-amyloid treatment available as a treatment option for the estimated 6.7 million people in the United States who live with Alzheimer’s disease.

The new therapy, given intravenously, appears to slow cognitive decline by attaching and removing a protein that accumulates into plaque in the brain. The recommendation now goes to the agency for full approval.

U-M experts are available to discuss the latest treatment and related issues.

Henry Paulson is the Lucile Groff Professor of Neurology for Alzeimer’s Disease at the U-M Medical School and director of the Michigan Alzheimer’s Disease Center. His research and clinical interests concern the causes and treatment of age-related neurodegenerative diseases, with an emphasis on polyglutamine diseases, Alzheimer’s disease and frontotemporal dementia. His lab also helped pioneer the use of gene silencing methods as potential therapy for the many neurological disorders caused by “toxic” mutant genes

“There is a widely accepted view that beta-amyloid is a critical early step in the Alzheimer’s cascade,” Paulson said. “Amyloid is clearly necessary but not sufficient to cause disease. The success of anti-amyloid therapies, such as donanemab, is a great step for the field. However, it also underscores the importance of pursuing other paths to disease-modifying treatment beyond amyloid: tau, immune pathways and vascular contributions, among others.”

Contact: [email protected]

Scott Roberts, professor of health behavior and health education at the School of Public Health, studies ethical and psychosocial issues involved in disclosing genetic test information. He expects a new option to lead to more genetic testing such as Apolipoprotein E genotyping, which can assess susceptibility to Alzheimer’s disease. His recent research evaluated the risks, benefits and potential consequences of APOE genotyping on patients, families and health care providers.

“APOE genotyping can be helpful for treatment decision-making for both of the new drugs, given that E4 carriers are at elevated risk for side effects such as microbleeds. I would expect more genetic testing to be done in this context,” said Roberts, who also pointed out the significance of the development.

The approval of donanemab “stands in stark contrast to 2021 FDA consideration of Aduhelm, which was approved despite an advisory panel’s concerns,” he said. “After going well over a decade with no FDA approval of any AD therapies, we should soon now have FDA approval of three therapies within the past three years, a sign of accelerated progress in AD clinical trials.

“These new anti-amyloid therapies are not widely accessible, given high costs, challenges of administration such as needing to be given via IV infusion, and the need for neuroimaging to confirm patient eligibility and monitor for side effects.”

Contact: [email protected]

Judith Heidebrink is the Richard D. and Katherine M. O’Connor Research Professor of Alzheimer’s Disease, professor of neurology and co-division chief of the Cognitive Disorders Program at the U-M Medical School. She has been involved in collaborative clinical trials in dementia for more than 20 years, including phase I-III studies focusing on the prevention and treatment of Alzheimer’s dementia.

In addition, she led U-M’s participation in the Alzheimer’s Disease Neuroimaging Initiative since the inception of this longitudinal observational study of brain imaging and other biomarkers in the progression from normal aging to dementia.

“I am hopeful that yesterday’s favorable review of donanemab by the FDA advisory panel paves the way to ultimate FDA approval,” Heidebrink said. “This will expand our ability to provide disease-modifying anti-amyloid therapies while the field continues to develop other treatments looking at a broad range of mechanisms.”

Contact: [email protected]