On 11 March, the Food and Drug Administration (FDA) announced the availability of a revised draft guidance for industry entitled “Early Alzheimer’s Disease: Developing Drugs for Treatment.” This newly proposed draft guidance is a revision of the prior draft issued on February 16, 2018. This guidance document is being distributed for comment purposes only. The final version is intended to assist sponsors in the clinical development of drugs for the treatment of the stages of sporadic Alzheimer’s disease (AD) that occur before the onset of overt dementia. These stages are collectively referred to as “early AD” in this guidance; however, it is recognised that AD occurs on a continuum and patients in the last stage of early AD (i.e., late Stage 3) and patients with AD in the earliest stages of overt dementia (i.e., early Stage 4) may not differ significantly in clinical presentation.
This document provides an overview on the FDA current thinking on diagnostic criteria and clinical staging of AD to inform enrolment in clinical trials and the selection of appropriate endpoints in clinical trials. This latest version of the FDA’s draft guidance introduced a new subsection dedicated specifically to surrogate endpoints and accelerated approval. FDA states in the document that there has been an effort to incorporate in clinical trials the use of biomarkers reflecting underlying AD pathophysiological changes and the enrolment of people with AD at earlier stages of the disease. "Clinical trials showing an effect on a surrogate endpoint that is determined to be reasonably likely to predict clinical benefit can be the basis for accelerated approval, including for drugs intended for the treatment of AD. For example, in certain circumstances, FDA has considered a reduction of the brain amyloid beta burden, as assessed by positron emission tomography, to be a surrogate endpoint that is reasonably likely to predict clinical benefit."