PND115 - A COMPARISON OF FDA AND EMA GUIDANCE ON MEDICINES FOR THE TREATMENT OF ALZHEIMER’S DISEASE

Abstract

Both the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) revised their clinical development guidelines on medicines for the treatment of Alzheimer’s disease (AD) in early 2018. This study aims to compare the two guidelines to identify what may reflect regional values and preferences. Draft guidance for treatment of AD by the FDA and EMA were examined and analyzed by two reviewers. A table was created to evaluate alignment between aspects of each guidance offered by two regulatory agencies. There is general alignment between the FDA and EMA on defining the stages of AD, diagnostic criteria, and efficacy endpoints, however, certain variations exist. The EMA guidance provides detailed recommendations on defining efficacy endpoints along the AD continuum, trial design features, and standards for outcome assessments, whereas the FDA guidance provides a brief overview of recommendations with an emphasis on endpoints for early AD clinical trials. For example, the FDA defines six stages of dementia ranging from asymptomatic with pathophysiologic changes to severe overt dementia, while the EMA adopts the IWG and NIA-AA three stages of AD (preclinical AD, prodromal/MCI due to AD, AD dementia), creating a challenge to align recommendations for stage-specific efficacy endpoints. In addition, the EMA guidance contains additional sections, including the role of biomarkers, statistical considerations, and safety evaluations, while the FDA mentioned the potential for biomarkers in asymptomatic patients to serve as the basis for accelerated approval. FDA and EMA guidance for treatment of AD were similar in defining clinical benefit for early AD. The EMA guidance was more comprehensive with considerations for disease modifying treatments and outcome measures that reflect a clinically meaningful benefit for patients. FDA and EMA collaboration could be helpful in standardizing recommendations for industry in achieving clinical benefit through innovative trial design and targeted treatment effects.