Efficacy of solanezumab in patients with mild or moderate Alzheimer's disease: Pooled analyses findings from two phase III studies

Abstract

Solanezumab, a humanized monoclonal antibody that binds the mid-domain of soluble amyloid beta (A b) peptide, was developed for treatment of Alzheimer's disease (AD). Two identically-designed Phase 3 trials were conducted. Pooled analyses findings from two double-blind, placebo-controlled Phase 3 trials are presented Participants with mild (baseline Mini-Mental State Examination [MMSE] score 20–26) to moderate (MMSE score 16–19) AD were randomized 1:1 to 400 mg solanezumab or placebo infusion every 4 weeks for 80 weeks. Primary outcomes of cognition and daily functioning were assessed using several Alzheimer's Disease Assessment Scale-Cognitive subscales (ADAS-Cog) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) inventory, respectively. Additional measures of efficacy and safety were also assessed. Mixed model repeated measures (MMRM) analyses were conducted for each of the efficacy measures. In the mild population, approximately 34 % less cognitive decline (ADAS-Cog 11, ADAS-Cog 14 and MMSE) was observed in the solanezumab versus placebo group (Table). In this population, there was no significant difference in overall functional decline between solanezumab versus placebo, but using a subset of instrumental ADLs (ADCS-iADL), the difference reached statistical significance (Table). In the moderate population, there were no between-treatment group differences in any cognitive or functional measure. In both mild and moderate populations, there were no significant treatment group-differences for Clinical Dementia Rating Scale-Sum of Boxes, Neuropsychiatric Inventory or quality of life measures. No individual serious adverse event was common, but significant treatment group differences were observed for Angina Pectoris, Congestive Heart Failure and Syncope (more common with solanezumab), and for Behavioral and Psychiatric Symptoms of Dementia and Mental Status Change (more common with placebo). Frequencies of treatment-emergent amyloid-related imaging abnormalities-edema/effusions (1.1% vs. 0.5%) and -hemosiderin deposition (9.1% vs. 7.3%) were greater with solanezumab, but not significantly different from placebo. There were no significant treatment-group differences in treatment-emergent changes in vital signs or laboratory measures. In a pooled analysis of solanezumab trial data, solanezumab reduced cognitive and functional decline in the mild but not the moderate AD population. Safety findings supported a favorable risk/benefit ratio.