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Sevigny et al. RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐CONTROLLED, PHASE IB STUDY OF ADUCANUMAB (BIIB037), AN ANTI‐AB MONOCLONAL ANTIBODY, IN PATIENTS WITH PRODROMAL OR MILD ALZHEIMER’S DISEASE: INTERIM RESULTS BY DISEASE STAGE AND APOE4 STATUS. AAN 2015
Objective: Aducanumab (BIIB037) is a human monoclonal antibody selective for aggregated forms of beta‐amyloid peptide being investigated as a disease‐modifying treatment for AD.
Background: This Phase 1b study is evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of aducanumab in patients with prodromal or mild AD.
Design/Methods: Patients included in this multicenter, randomized, double‐blind, placebo‐controlled, multiple‐dose study (PRIME; NCT01677572) were aged 50‐90 years, had a positive florbetapir (18F‐AV‐45) PET scan, and met clinical criteria for prodromal or mild AD. During the double‐blind, placebo‐controlled phase, patients received aducanumab or placebo once every 4 weeks for 52 weeks. In a staggered, ascending‐dose design, patients were randomized to 1 of 7 treatment arms stratified by ApoE4 status (carrier/non‐carrier). We present results from an interim analysis (after subjects in all arms completed at least the Week 26 visit) on safety and change in florbetapir PET signal by disease stage and ApoE4 status.
Results: Patients (N=166) were randomized to placebo (n=40), 1 (n=31), 3 (n=33), 6 (n=30) or 10 (n=32) mg/kg aducanumab. Of 165 patients dosed, 65% were ApoE4 carriers (35% non‐carriers) and 41% had prodromal AD (59% mild). The incidence (based on MRI) of the most common AE (amyloid‐related imaging abnormalities [ARIA]) was dose‐ and ApoE4‐status?dependent (for ARIA‐edema or ‐microhemorrhage or ‐hemosiderosis: ApoE4 carriers, 11%, 14%, 43% and 65% for 1, 3, 6 and 10 mg/kg aducanumab, respectively, versus 8% for placebo; ApoE4 non‐carriers, 8%, 18%, 11%, and 17% versus 0%). Treatment‐related dose‐ and time‐dependent reductions in brain beta‐amyloid plaque (shown by SUVR reduction) at Weeks 26 and 54 were consistent across mild and prodromal subgroups and across ApoE4 carriers and non‐carriers within the doses tested.
Conclusions: ARIA was the main safety and tolerability finding and was dose‐and ApoE4‐dependent. Aducanumab reduced beta‐amyloid plaque across mild and prodromal stages, and ApoE4 carriers and non‐carriers.