Profiling lecanemab as a treatment option for Alzheimer’s disease

ABSTRACT

Introduction

In July 2023, the U.S. Food and Drug Administration (FDA) granted full approval to lecanemab for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD dementia. Considering the limited treatment options for AD, the approval of lecanemab offers hope and opens the door for other disease-modifying therapies in the pipeline.

Areas covered

In this review, the authors summarize the FDA treatment guidelines, other anti-amyloid agents, and drug information relevant to prescribers, such as pharmacology and pharmacokinetics. Relevant clinical trial outcomes are discussed along with their significance and controversies.

Expert opinion

While questions remain about the magnitude of lecanemab’s clinical impact, its approval signifies major progress in addressing the underlying pathology of AD. The authors have confidence in lecanemab as a promising treatment option and foresee exciting advancements on the 5-year horizon. Yet, further research is needed regarding trials beyond 18 months, post-marketing surveillance, and lecanameb in combination with existing treatments and lifestyle interventions.

KEYWORDS:

• Dementia
• Alzheimer’s disease
• Alzheimer disease
• lecanemab
• anti-amyloid monoclonal antibodies
• aducanumab
• donanemab

Article highlights

• Alzheimer’s disease (AD), a condition common in the elderly, is expected to become more common as the U.S. population ages.

• Lecanemab is the first fully FDA approved treatment for mild cognitive impairment (MCI) due to AD or mild AD dementia.

• Other anti-amyloid monoclonal antibodies have reached phase III clinical trials but were withdrawn from clinical development due to ineffectiveness or safety concerns.

• Aducanumab, another anti-amyloid monoclonal antibody, received accelerated approval from the FDA.

• Data from clinical trials shows that lecanemab significantly reduced amyloid accumulation in the brain, and that re-accumulation is minimal in the months after discontinuation.

• Although lecanemab significantly reduced cognitive decline in the trial treatment group, there remains controversy over whether the clinical effect is meaningful.

Declaration of interest

G Grossberg serves as a consultant to Acadia, Avanir, Axona, Axsome, Biogen, BioXcel, Eisai, Eli Lilly and Company, 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.