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

Alzheimers Dement. 2016 Feb;12(2):110-120. doi: 10.1016/j.jalz.2015.06.1893. Epub 2015 Aug 1.


Introduction: EXPEDITION and EXPEDITION2 were identically designed placebo-controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid-β peptide, on cognitive and functional decline over 80 weeks in patients with mild-to-moderate 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 + EXPEDITION2) mild AD population were performed.

Results: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. Baseline-to-endpoint changes did not differ between treatment groups for Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale, basic items of the ADCS-ADL, and Clinical Dementia Rating Sum of Boxes. 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.

Keywords: Amyloid-β peptide; Clinical trial; Cognition; EXPEDITION; Function; LZAM; LZAN; Mild Alzheimer's disease; Monoclonal antibody; Phase 3; Safety; Solanezumab; Target engagement.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cognition / drug effects*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Neuropsychological Tests / statistics & numerical data*
  • Severity of Illness Index
  • Treatment Outcome


  • Amyloid beta-Peptides
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • solanezumab