Solanezumab

Analyst Outlook

Eli Lilly’s solanezumab is the most clinically advanced amyloid-beta monoclonal antibody (MAb) in the

pipeline, having already undergone two global Phase III trials. While these studies, EXPEDITION 1 and

EXPEDITION 2, failed to provide sufficient evidence to support regulatory filing in mild to moderate

Alzheimer’s disease, they did demonstrate a sign of efficacy in mild Alzheimer’s disease, which Eli Lilly

is now investigating in a third study, EXPEDITION 3. Although this third trial could delay any potential

regulatory filing by several years, it will provide more conclusive evidence for the drug’s disease-
modifying properties and cognitive benefit in the more appropriate mild Alzheimer’s disease

population. In addition, Eli Lilly is extending solanezumab’s efficacy evaluation to the prodromal

population and to patients at risk of developing Alzheimer’s disease. However, although the current

data is statistically significant, there is a danger that solanezumab’s slight effect on slowing cognitive

decline is not necessarily relevant for clinical practice.

Drug Overview

Solanezumab is a humanized version of mouse antibody m266, an immunoglobulin G1 MAb that

recognizes a central primary sequence epitope on amyloid-beta (Alzforum, 2015). Solanezumab is

believed to bind specifically to soluble amyloid-beta and thereby alters the sticky characteristics of

this peptide (Lemere and Masliah, 2010). The binding and removal of soluble amyloid-beta by

solanezumab could lead to the dissolution of amyloid-beta plaques, which may result in slowing

disease progression.

Eli Lilly has already completed two global Phase III trials of solanezumab in patients with mild to

moderate Alzheimer’s disease. However, the failure of solanezumab to meet its primary endpoints in

these pivotal trials has forced Eli Lilly to redesign its clinical program and instead target the mild

Alzheimer’s disease subset. This setback means that solanezumab is unlikely to reach the market

before 2017.

Following the discontinuation of intravenous bapineuzumab (Johnson & Johnson/Pfizer), solanezumab

is now the leading amyloid-beta antibody in clinical development.