Efficacy and Safety of Intravenously Administered Solanezumab in the Treatment of Patients with Mild-to-Moderate Alzheimer's Disease

Pooled results from two phase 3 studies (EXPEDITION and EXPEDITION2) evaluating the efficacy and safety of intravenously administered solanezumab suggest that it may improve cognition and activities of daily living for patients with mild Alzheimer’s disease, according to research presented at the 65^th Annual Meeting of the American Academy of Neurology.

Solanezumab is a humanized monoclonal antibody that has been specifically designed to bind to the mid-domain of soluble, monomeric forms of amyloid beta peptide, allowing it to be cleared before it clumps together to form beta-amyloid plaques. It is currently under development for the treatment of patients with Alzheimer’s disease.

Ann Hake, MD, of Indiana University Medical Center in Indianapolis, Indiana, and colleagues conducted two randomized, placebo-controlled phase 3 studies involving 2,052 patients with mild-to-moderate Alzheimer disease to evaluate the efficacy and safety of solanezumab (400 mg) administered intravenously once every four weeks for a total of 80 weeks. The investigators used the Alzheimer’s Disease Assessment Scale — Cognitive subscale (ADAS-Cog) to assess patient cognition, and the Alzheimer’s Disease Cooperative Study—Activities of Daily Living (ADCS-ADL) inventory was used to assess patients' daily functioning.

In the EXPEDITION trial, in the overall mild-to-moderate Alzheimer’s disease population, no statistically significant difference in solanezumab-treated patients was observed for either the ADAS-Cog11 or ADCS-ADL scores when compared with placebo (p=0.312 and p=0.931, respectively). However, the results of a prespecified secondary analysis of the subpopulation of patients with mild Alzheimer’s disease, indicated that the difference in the ADAS-Cog14 was highly statistically significant (p=0.006). Unfortunately, using the ADAS-Cog14 for the mild subpopulation did not produce statistically significant results in the EXPEDITION2 trial (p=0.120).

When pooling the results of both trials together, however, solanezumab did appear to result in a statistically significant improvement in cognition and also improved instrumental ADLs for patients with mild Alzheimer’s disease. Instrumental ADLs were also improved in patients with mild Alzheimer’s disease in the EXPEDITION2 trial results alone.

“We believe these results demonstrate a slowing of cognitive decline in patients with mild Alzheimer's disease treated with solanezumab and will help to advance the understanding of the amyloid hypothesis,” the authors concluded. An additional phase 3 trial of solanezumab in patients with mild Alzheimer's disease will be conducted to provide additional information.

This study was supported by Eli Lilly and Co.