Post-Hoc Analysis of Early AD Subjects Meeting Phase 3 Entry Criteria in PRIME, a Phase 1b Study of the Anti-Amyloid Beta Antibody Aducanumab (BIIB037) (P4.007)

OBJECTIVE: To report interim data from the ongoing Phase 1b study (PRIME) in patients with Early Alzheimer’s Disease (AD) with similar characteristics to Phase 3 entry criteria.BACKGROUND: Aducanumab (BIIB037), a human anti-amyloid beta (Aβ) monoclonal antibody, is being investigated as a disease-modifying treatment for AD. Interim PRIME results demonstrated target engagement, pharmacodynamic effect, and a clinical effect on exploratory outcomes; the main safety/tolerability findings were amyloid-related imaging abnormalities (ARIA).DESIGN/METHODS: In the double-blind, placebo-controlled, multiple-dose PRIME study (NCT01677572), patients (aged 50-90 years; positive florbetapir [Amyvid™] PET scan; clinical criteria for prodromal or mild AD) received aducanumab or placebo once every 4 weeks for 52 weeks in 9 arms stratified by ApoE carrier e4 status. The primary endpoint was safety and tolerability; secondary endpoints included change from baseline to Week 26 in amyloid PET. Changes in clinical measures of cognitive decline (CDR-SB/MMSE) were exploratory endpoints. A subpopulation of patients with Early AD was defined by: CDR Global Score 0.5; CDR memory domain score ≥0.5; MMSE score ≥24. We report post-hoc analysis of interim data in the Early AD subpopulation for arms 1-7 (1, 3, 6, and 10 mg/kg aducanumab and placebo arms).RESULTS: Of 165 patients dosed in PRIME, 92 had similar characteristics to Phase 3 entry criteria; 66 had prodromal and 26 mild AD. Consistent with overall PRIME results, we observed dose-dependent reduction in amyloid plaque burden at 6 months and 1 year, and dose-dependent slowing of cognitive decline in exploratory clinical endpoints (CDR-SB/MMSE) at 1 year. ARIA-E was the main safety/tolerability finding.CONCLUSION: Results in the PRIME Early AD subpopulation were highly consistent with results in the overall PRIME population, supporting selection of the target study population for the Phase 3 trials.Study support: funded by Biogen. Disclosure: Dr. Viglietta holds stock and/or stock options in Biogen Idec. Dr. Miao has received personal compensation for activities with Biogen as an employee. Dr. Miao holds stock and/or stock options in Biogen, which sponsored research in which Dr. Miao was involved as an investigator. Dr. Chen holds stock and/or stock options in Biogen Idec. Dr. O9Gorman holds stock and/or stock options in Biogen Idec. Dr. Williams holds stock and/or stock options in Biogen Idec. Dr. Ling has received personal compensation for activities with Biogen as an employee. Dr. Ling holds stock and/or stock options in Biogen, which sponsored research in which Dr. Ling was involved as an investigator. Dr. Sevigny holds stock and/or stock in Biogen Idec.