On February 16, 2018, FDA issued draft guidance on Early Alzheimer’s Disease (AD): Developing Drugs for Treatment. This draft guidance revises the draft guidance related to treating AD from February 2013. FDA intends the new draft guidance to assist sponsors in the clinical development of drugs for AD that occurs before the onset of overt dementia.

FDA recommends basing eligibility for efficacy trials in AD at least in part on current consensus diagnostic criteria. According to FDA, important findings applicable to the categorization of AD along its continuum of progression include the presence of pathophysiological changes as measured by biomarkers, the presence or absence of detectable abnormalities on sensitive neuropsychological measures, and the presence or absence of functional impairment.

FDA identifies four categories as conceptually useful for the design and evaluation of clinical trials in different stages of AD: Stage 1 (characteristic pathophysiologic changes of AD but no evidence of clinical impact), Stage 2 (characteristic pathophysiologic changes of AD and subtle detectable abnormalities on sensitive neuropsychological measures, but no functional impairment), Stage 3 (characteristic pathophysiologic changes of AD, subtle or more apparent detectable abnormalities on sensitive neuropsychological measures, and mild but detectable functional impairment), and Stage 4 (overt dementia). FDA discusses clinical endpoints for early AD trials in patients with stage 1, 2, or 3.

FDA states that the use of a time-to-event survival analysis approach would be an acceptable primary efficacy measure in clinical trials in early AD, and that sponsors considering such an approach should discuss their plans with FDA early in development.