EFFECT OF SOLANEZUMAB ON BIOMARKERS OF NEURODEGENERATION IN THE EXPEDITION3 TRIAL IN MILD ALZHEIMER DISEASE

Solanezumab is a humanized monoclonal antibody that preferentially binds soluble amyloid. Its efficacy in treating mild Alzheimer disease (AD), at an intravenous dose of 400mg administered every four weeks, was evaluated in a phase 3, double-blind trial in participants randomized to placebo (n=1072) or solanezumab (n=1057) (EXPEDITION3). Alongside clinical scales, volumetric magnetic resonance imaging (vMRI; in all patients) and cerebrospinal fluid (CSF; in a subset of patients) biomarkers reflecting neurodegenerative processes associated with AD were measured with the aim of assessing solanezumab's effects on longitudinal changes in these markers. 3DT1 scans for vMRI analysis (n=1043 (placebo) and N=1038 (solanezumab)), and CSF samples (n=188–208/arm, depending on the assay), were obtained at baseline and following 80 weeks of treatment. MRI scans were analyzed for hippocampal, entorhinal cortex, ventricular and whole brain volumes using Freesurfer-based methods. Total tau (t-tau) and phospho-tau 181 (p-tau181) concentrations were determined from the CSF samples using validated INNOTEST(R) ELISA assays. An ANCOVA analysis of each biomarker compared the 80-week least square mean change in placebo and solanezumab groups. The right hippocampal volume achieved a nominally statistically significant reduction in the rate of atrophy (p=0.032), corresponding approximately to a 6.7% slowing. Directionally, the other vMRI variables evidenced a reduced rate of atrophy in the solanezumab arm relative to the placebo arm, but these trends did not reach statistical significance (0.077