Still grasping at straws: donanemab in Alzheimer’s disease

ABSTRACT

Introduction

Alzheimer’s disease is the leading cause of disability and poor health, takes a huge emotional and financial burden on family caregivers, and is costly. Donanemab (LY3002813) is a new monoclonal antibody that uniquely targets Aβ(p3-42), a pyroglutamate form of Amyloid-β (Aβ) exclusively found in plaques.

Areas covered

The phase 2 trial of donanemab in participants with early symptomatic Alzheimer’s disease, TRAILBLAZER-ALZ. Donanemab reduced cerebral plaque but not tau load and only marginally improved the primary outcome of cognition and activities of daily living (p = 0.04) without altering individual measures of these.

Expert opinion

In TRAILBLAZER-ALZ, anticholinesterase use was given at the beginning but not the end of the trial, and thus, it is not known whether changes in this or other medicines were involved in the outcome with donanemab. Tau load (measured with flortuacipir PET) may be a biomarker of cognition but was not altered by donanemab. As there is no clear evidence that removing cerebral amyloid plaques with Aβ antibodies, such as donanemab, improves cognition and the activities of daily living in Alzheimer’s disease, clinical trials with these agents should be abandoned, and more time and money should spend on further investigating the underlying cause of Alzheimer’s disease.

KEYWORDS:

• Alzheimer’s disease
• amyloid β
• clinical trial
• cognition
• donanemab
• TRAILBLAZER-ALZ

Declaration of interest

The authors have 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

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.