Featured Article Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients

Introduction: EXPEDITION and EXPEDITION2 were identically designed placebo-controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid-b peptide, on cognitive and functional decline over 80 weeks in patients with mild-tomoderate Alzheimer’s disease (AD). Primary findings for both studies have been published. Methods: Secondary analyses of efficacy, biomarker, and safety endpoints in the pooled (EXPEDTION 1 EXPEDITION2) mild AD population were performed. Results: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n 5 659) versus placebo (n 5 663), measured by Alzheimer’s Disease Assessment Scale Cognitivesubscale,Mini-MentalStateExamination,andAlzheimer’sDiseaseCooperativeStudy–Activities of Daily Living functional scale Instrumental ADLs. Baseline-to-endpoint changes did not differbetweentreatmentgroupsforAlzheimer’sDiseaseCooperativeStudy–ActivitiesofDailyLiving functionalscale,basicitemsoftheADCS-ADL,andClinicalDementiaRatingSumofBoxes.Plasma/ cerebrospinal fluid biomarker findings indicated target engagement by solanezumab. Solanezumab demonstrated acceptable safety. Efficacy findings for the moderate AD population are also provided. Discussion: These findings describe solanezumab effects on efficacy/safety measures in a mild AD population. Another phase 3 study, EXPEDITION3, will investigate solanezumab’s effects in a mild AD population. 2016 Eli Lilly and Company, Indianapolis, IN. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).