Grasping at straws: the failure of solanezumab to modify mild Alzheimer’s disease

ABSTRACT

Introduction: The amyloid-beta (Aβ) cascade hypothesis is that reducing Aβ levels in the brain will be beneficial in the treatment of Alzheimer’s disease. Solanezumab is a humanized analog of a murine antibody that selectively targets the central domain of the soluble form of Aβ. In the EXPEDITION 1 and 2 Phase 3 clinical trials, solanezumab was shown to be ineffective in subjects with mild-to-moderate Alzheimer’s disease, and to have no effect on brain Aβ burden.

Areas covered: This evaluation considers the secondary analysis of (EXPEDITION 1 and 2), which led to the EXPEDITION 3 trial of solanezumab in subjects with mild Alzheimer’s disease, and the results of EXPEDITION 3.

Expert opinion: The secondary analysis of EXPEDITION 1 and 2 was limited to mild Alzheimer’s disease, and showed improvements on some scales, but not others. This analysis did not report data on Aβ burden. In my opinion, this was a questionable basis to undertake a further phase trial with solanezumab. The EXPEDITION 3 trial of solanezumab in subjects with mild Alzheimer’s disease was terminated early for ineffectiveness. With hindsight, solanezumab should have been discontinued after EXPEDITION 1 and 2, especially as it had not been shown to reduce Aβ burden.

KEYWORDS:

• Alzheimer’s disease
• amyloid-β
• EXPEDITION clinical trials
• solanezumab

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

One of the reviewers on this article has acted as a chair and project leader for solanezumab trails and has been an author on papers publishing on the drug. Additional peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This article was not funded.