Towards a more representative Alzheimer’s disease clinical trial: Ethnic differences in underlying pathology call for demographic consideration in drug label development

Abstract

AbstractBackgroundClinical trials have historically underrepresented racial and ethnic minority groups, often exhibiting sub‐par external validity and representing a population that is exceedingly White and not Hispanic or Latino (H/L). An understanding of the underlying pathology and safety profile of racial and ethnic minority groups is important to interpretation of clinical trial results and the development of accurate drug labels. T3D Therapeutics’ Phase 2 PIONEER Study (evaluating the safety and efficacy of lead candidate drug T3D‐959) provides a unique opportunity to examine safety data in an Alzheimer’s disease (AD) trial with a relatively high percentage of H/L subjects.MethodPIONEER is an ongoing randomized, double‐blind, placebo‐controlled, Phase 2 trial involving 256 mild to moderate AD patients dosed orally once‐a‐day for 24‐weeks. Exploratory analyses examine ethnic differences in medical data including screen fail reasons, medical history, and adverse events.ResultMedical history and screen fail reason data suggest differences in underlying pathology between H/L and non‐H/L subjects. For example, data show a higher rate of screen failure due to elevated HbA1c among H/L subjects vs. non‐H/L subjects. Conversely, H/L subjects show lower rates of surgical and medical procedures as well as other medical history events. Rates of reporting adverse events as well as types of adverse events reported are also significantly different between the two groups.ConclusionEthnic differences drive differential safety profiles across study subjects, challenging the applicability of non‐H/L clinical trial data to the H/L population. Our data suggest that more weight should be put on ethnicity and other demographic characteristics in developing drugs’ side effects listings. We stress that ethnic background should play a larger role in label development, and urge the clinical trial community to continue in the direction of enrolling underrepresented racial and ethnic minority groups.