How promising are the latest monoclonal antibodies targeting amyloid-β for the treatment of early Alzheimer’s disease?

ABSTRACT

Introduction

Monoclonal antibodies targeting amyloid-β are the first disease-modifying treatments for Alzheimer disease to have received FDA-approval. There are three different drugs approved or pending FDA-approval: aducanumab, lecanemab, and donanemab. These three drugs are each in different stages of regulatory approval by the FDA.

Areas covered

We discuss the development of these drugs, the data regarding their clinical efficacy, their dosing regimens, and side effects. In addition, we examine pragmatic issues with their potential implementation as common treatments to slow the rate of decline in Alzheimer disease, and what unanswered questions remain regarding this new class of drugs.

Expert opinion

We conclude that these new monoclonal antibodies that target amyloid-β represent a genuine advance in the treatment of Alzheimer disease. However, questions remain regarding their clinical significance. Additionally, it is presently unclear which patients would most benefit from these expensive drugs given the risk of side effects and the logistical difficulties concerning administration and the determination of eligibility.

KEYWORDS:

• Aducanumab
• lecanemab
• donanemab
• Alzheimer disease
• dementia

Article highlights

• Monoclonal antibodies have emerged as the first disease-modifying treatments for Alzheimer disease, although these medications must be started early in the course of the disease.

• There are three different drugs available, in different stages of regulatory approval, with varying levels of evidence to support their effectiveness.

• Overall, these drugs are a promising step-forward, but there are many pragmatic concerns that may prevent immediate and widespread adoption, especially with regard to cost, whether patients qualify, administration, and side-effects.

• Amyloid-related imaging abnormalities (ARIA) are the most important novel concern with these new drugs, which may have to be monitored with serial magnetic-resonance imaging (MRI) during treatment.

• These three drugs, aducanumab, lecanemab, and donanemab, have all been tested in large, randomized, double-blind, placebo-controlled trials. However, as of this writing, only lecanemab has full FDA approval.

Declaration of interest

G Grossberg serves as a consultant to Acadia, Avanir, Axona, Axsome, Biogen, BioXcel, Eisai, Eli Lilly, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.