Amyloid and APOE Status of Screened Subjects in the Elenbecestat MissionAD Phase 3 Program

Background/Objectives Elenbecestat, an oral BACE-1 inhibitor that has been shown to reduce A beta levels in cerebrospinal fluid, was investigated in two global phase 3 studies in early AD. Here we report on differences observed in characteristics of APOE epsilon 4 and amyloid positive subjects in the large screening cohort. Design Screening was performed in 5 sequential tiers over a maximum of 80 days, as part of placebo controlled, double blind phase 3 studies. Setting Subjects were evaluated at sites in 7 regions (29 countries). Participants Overall, 9758 subjects were screened. Intervention All screened subjects that were eligible received either placebo or 50 mg QID elenbecestat post randomisation. Measurements Gender, disease staging, APOE epsilon 4 status, amyloid status, amyloid positron emission tomography (PET) standard uptake value ratio (SUVr) and amyloid PET Centiloid (CL) values were determined for screened subjects; by country and region. Results In this program, 44% of subjects were APOE epsilon 4 positive. Frequency of females was similar in both APOE epsilon 4 positive and negative groups. However, early mild AD subjects were slightly higher in the APOE epsilon 4 positive group compared with the APOE epsilon 4 negative group. 56% of subjects were amyloid positive. The mean age in the amyloid positive group was slightly higher than the amyloid negative group. The gender distribution was similar between amyloid groups. A lower number of mild cognitive impairment was observed in the amyloid positive group along with a higher number of early mild AD. APOE epsilon 4 positive subjects were higher in amyloid positive group compared to the amyloid negative group. China had the lowest APOE epsilon 4 and amyloid positivity rates with Western Europe and Oceania performing best. Subjects received florbetapir, florbetaben or flutemetamol amyloid PET tracer. Amyloid negative and positive subjects CL values were normally distributed around their respective means of 1.5 CL and 83 CL. However, there was an appreciable overlap in the 20-40 CL range. Conclusions In this large cohort of cognitively impaired subjects, subject demographics characteristics were comparable regardless of APOE genotype or amyloid positivity. APOE epsilon 4 positivity and amyloid positivity varied by country and by geographical region.

Automated summary

The study found differences in characteristics of APOE epsilon 4 and amyloid positive subjects in the early AD screening cohort, with variation in positivity rates by country and geographical region.