[3-11-2024] Today, FDA issued a revised draft guidance, Early Alzheimer’s Disease: Developing Drugs for Treatment Guidance for Industry.

Once finalized, the guidance will provide recommendations to help drug companies developing medicines to treat patients with early stages of Alzheimer’s disease that occur before the onset of overt dementia.

“FDA is committed to reducing the burden of Alzheimer’s disease,” said Teresa Buracchio, M.D., director of CDER’s Office of Neuroscience. “This guidance document provides the agency’s current thinking about diagnostic criteria and clinical staging and the selection of appropriate outcome measures, including the use of surrogate endpoints, for the early stages of Alzheimer’s Disease.”

Alzheimer’s disease is an irreversible, progressive brain disorder affecting more than 6.5 million Americans. While the specific causes of Alzheimer’s are not fully known, it is characterized by changes in the brain—including the formation of amyloid beta plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections.

Patients with early stages of Alzheimer’s disease may have minimal or no signs of cognitive and functional deficits, such as memory loss, that are typically associated with later stages of the disease. For patients in earlier stages, drug developers may consider the use of surrogate endpoints. A surrogate, or substitute, endpoint can be a laboratory measurement, medical imaging, physical sign, or other assessment that is not itself an indication of clinical benefit but is reasonably likely to predict clinical benefit.

Drug developers considering the use of a surrogate endpoint as the primary measure of effect should discuss their plans with FDA early in development. The agency strongly supports and encourages continued research in understanding the role of surrogate endpoints and stresses their potential importance in the successful development of effective treatments for the earliest stages of Alzheimer’s disease.