Pharmacokinetic evaluation of donanemab for the treatment of Alzheimer’s

ABSTRACT

Introduction

Donanemab is a humanized monoclonal antibody that significantly reduces cerebral amyloid plaques in Alzheimer’s Disease (AD). It can delay disease progression and cognitive decline, making it one of the most promising disease-modifying treatments in the current treatment landscape.

Areas Covered

This paper covers the current literature available on pharmacokinetics, pharmacodynamics, safety, and tolerability of donanemab. Publications from PubMed and Google were reviewed. A summary of regulatory approvals and current clinical data is also provided.

Expert Opinion/Commentary

Donanemab as a therapy for AD has more effective disease-modifying effects compared to lecanemab. Donanemab appears generally well-tolerated; however, it may have higher rates of severe side effects, such as amyloid-related imaging abnormalities (ARIA), that could lead to death. Guidelines for frequency of MRI monitoring for ARIA/safety are pending but will be integral to determining its use. Despite some limitations, donanemab is expected to receive FDA approval, giving clinicians access to another disease-modifying drug. Overall, more data is needed about donanemab, especially relating to safety, efficacy, cost, and integration with other treatments, but its development signifies progress in AD treatment.

Plain Language Summary

Alzheimer’s Disease (AD) is a brain disorder that severely impacts memory, behavior, and thinking. The most common treatments manage symptoms but do not slow disease progression or improve function. Accumulation of proteins called amyloid-beta plaques in the brain are one of the main causes of the disease. Donanemab is an antibody that helps the body remove these plaques. This review summarizes what is currently known about the safety of donanemab, how it works, and the extent to which it can help people with AD.

Results suggest that donanemab significantly decreases the amount of plaques in the brain, delays disease progression, and improves cognition. Treatment can prevent reaccumulation of plaques for an extended period of time. There are some side effects associated with treatment, but they are generally manageable and resolve when the drug is stopped. In rare cases, more serious side effects were reported. These require careful monitoring and an evaluation of potential risk compared to benefit. Overall, current information on donanemab is extensive and shows promise. However, to help caregivers and people with AD make informed decisions on using the drug, further research is needed to fully explore donanemab’s safety, cost, and efficacy compared to other therapies in the same class.

KEYWORDS:

• Amyloid
• Alzheimer’s disease
• disease-modifying
• donanemab
• immunotherapy
• LY3002813
• pharmacokinetics

Article highlights

• Donanemab, a promising immunotherapy for Alzheimer’s disease, demonstrates significant reduction in existing brain amyloid plaques, which could potentially delay disease progression and cognitive decline.

• Clinical data analysis provides evidence of reducing brain amyloid levels by 40–50% and preventing plaque reaccumulation after treatment cessation.

• Potential advantages of donanemab over existing therapies include less frequent administration, lower cost, and treatment discontinuation upon amyloid clearance.

• Donanemab is generally well-tolerated with manageable side effects that resolve on discontinuation. However, it appears to have a slightly increased risk of severe side effects including amyloid-related imaging abnormalities that could lead to death.

• FDA approval of donanemab is anticipated in 2024, allowing for more treatment options for health-care professionals, patients, and their caregivers.

Declaration of interest

G Grossberg serves as a consultant to Acadia, Axsome, Biogen, BioXcell, Eisai, Genentech, Lilly, Lundbeck, Otsuka, Roche, 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is a co-founder of Recuerdo Pharmaceuticals. He has served as a consultant in the past for J&J, Diagenic, and Pfizer, and he currently consults for Cognito Therapeutics, GLG Group, SVB Securities, Guidepoint, Third Bridge, MEDACORP, Altpep, Vigil Neurosciences, and Eisai. He has received research support in the past from Warner-Lambert, Pfizer, Baxter, and Avid. He currently receives research support from the NIH and the Cure Alzheimer’s Fund. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.