Amyloid burden assessed by three amyloid PET tracers in the elenbecestat MissionAD Phase 3 program

Abstract

AbstractBackgroundEisai’s elenbecestat MissionAD Phase 3 studies in early Alzheimer’s disease (AD) screened a large cohort of nearly 10,000 subjects for eligibility.MethodScreening was performed in 5 sequential tiers, of which amyloid status was determined at tier 5. Three amyloid PET tracers were used: florbetapir, florbetaben, flutemetamol. PET scans were centrally read by trained raters who determined visually if subjects were amyloid positive (Aß+) or negative (Aß‐). Quantitative analysis calculated a mean composite SUVr using whole cerebellum as a reference region and were converted to centiloid values (CL) to combine data across tracers (Klunk et al., 2015; http://www.gaain.org/centiloid‐project).Result3259 subjects had amyloid PET status and SUVr data available; 53% were Aß+, 86% were MCI and 12% mild AD dementia (2% missing), 52% were female, and 45% of were APOE ɛ4 positive. 2452, 542, and 265 subjects were scanned using, florbetaben, flutemetamol, or florbetapir, respectively, of which 50%, 59%, and 65% were determined visually to be Aß+. Centiloid conversion combining the data for the tracers calculated a mean of 1.6 CL for Aß‐ subjects (n=1532) and 83.0 CL for Aß+ (n=1725). No differences were evident between the tracers; mean of 1.2 – 3.1 CL for Aß‐ subjects and 77.3 ‐ 84.1 CL for Aß+ subjects. No impact of gender was evident. 77% of the APOE ɛ4 positive subjects were Aß+, which increased the mean CL value by 9. Mild AD dementia subjects had a higher Aß+ rate compared with MCI (69% vs 52%), which increased the mean CL value by 10.ConclusionAß+ status of subjects was approximately 50%, even when assessed at the end of a screening cascade. Although florbetaben was used in 75% of the subjects, the data was consistent between the tracers when converted to CL. Aß‐ and Aß+ subjects SUVr were normally distributed with an appreciable overlap in the 20‐40 CL range.