Introduction

• Donanemab, a new treatment for Alzheimer’s disease developed by Eli Lilly, has received unanimous support from independent experts advising the United States Food and Drug Administration (USFDA), advancing it closer to clinical trials.
• The FDA advisory committee noted in a briefing document that "the potential risks of donanemab, when properly managed as directed in the labelling, are outweighed by the demonstrated benefits on clinical endpoints in those with Alzheimer’s disease (AD)."

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How do the Benefits of the Drug Stack Up Against Its Risks?

• Donanemab is designed specifically for individuals in the early stages of Alzheimer’s disease, with mild cognitive impairment or mild dementia.
• The drug significantly slows the progression of the disease, allowing patients to maintain their functional abilities for a longer period.
• According to the FDA's risk-benefit assessment, most amyloid-related imaging abnormalities (ARIA), such as brain bleeding and seizures, were non-serious and resolved or stabilized when the medication was discontinued.
• Proper labelling and clinical monitoring can mitigate major concerns, and post-authorization studies can provide further insights. Given the severity of Alzheimer’s disease and the limited availability of disease-modifying treatments, donanemab offers a substantial clinical benefit for AD patients, as per the FDA statement.

How Does It Work?

• Donanemab is a monoclonal antibody that targets the accumulation of amyloid beta protein in the brain, a key characteristic of Alzheimer’s disease.
• A phase 3 trial demonstrated that donanemab reduced cognitive decline in early Alzheimer's patients by 35.1% over 76 weeks. The trial included 1,736 participants, with 860 receiving the infusion every four weeks until the amyloid beta plaque was eliminated.
• The primary side effect of the drug is brain swelling or bleeding, which is generally asymptomatic. The study reported that 24% of participants experienced brain edema, while 19.7% had brain bleeding. There were three treatment-related deaths documented in the study