Regulatory Innovation and Drug Development for Early-Stage Alzheimer's Disease

Abstract

In reviewing new-drug applications for the treatment of Alzheimer's disease, the Food and Drug Administration (FDA) has maintained that claims of improved cognition should be accompanied by evidence of improvement in function. However, the premise that effective cognitive improvement will be manifested in the functional assessment of patients is untenable in the case of early-stage Alzheimer's disease, which is increasingly the target of drug-development efforts. We simply do not yet have drug-development tools that are validated to provide measures of function in patients with Alzheimer's disease before the onset of overt dementia. Improvement in function, moreover, could lag substantially behind cognitive improvement mediated by pharmacologic agents early in the course of the disease. In view of the devastating effects of this disease on patients and their families, along with its growing prevalence, innovative approaches to trial design and end-point selection are urgently needed, especially as the drug-development community turns its sights on early stages of the disease.