Great Britain has granted approval for Leqembi (lecanemab), a treatment designed for adults with mild cognitive impairment (MCI) and early-stage dementia caused by Alzheimer’s disease (AD), particularly in those who are either heterozygous for or non-carriers of the apolipoprotein E ε4 (ApoE ε4) gene.
Mechanism of Action
Lecanemab, a humanized monoclonal antibody targeting amyloid-beta (Aβ), specifically binds to and neutralizes toxic Aβ protofibrils—clumps of Aβ that contribute to the formation of plaques in the brain, which are characteristic of Alzheimer’s. By binding to these aggregates, lecanemab facilitates their removal from the brain, aiming to slow or halt the progression of cognitive decline associated with AD.
Approval Based on Clinical Trial Results
The decision to approve lecanemab was heavily influenced by data from the Clarity AD Phase 3 clinical trial.
This global, randomized, double-blind, placebo-controlled study demonstrated that lecanemab significantly met its primary endpoint by showing improvement from baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB) score at 18 months. Additionally, all key secondary outcomes were achieved with statistically significant results. The trial's findings supported the efficacy of lecanemab in treating early-stage Alzheimer’s.
Side Effects and Safety Profile
In the population studied in Great Britain, the most common adverse effects associated with lecanemab included infusion-related reactions, amyloid-related imaging abnormalities with hemorrhage (ARIA-H), falls, headaches, and amyloid-related imaging abnormalities with cerebral edema (ARIA-E). These side effects were consistent with the known safety profile of the drug from clinical trials.
Alzheimer’s Disease in the United Kingdom
Alzheimer’s disease is a leading cause of dementia, affecting between 60% and 70% of the estimated 982,000 people living with dementia in the United Kingdom. As the population continues to age, these figures are expected to rise, increasing the need for effective treatments like lecanemab.
Collaboration for Accessibility
Eisai, the company leading the global development and regulatory processes for lecanemab, is collaborating with the National Institute for Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC), and the National Health Service (NHS) to ensure that the medication becomes available to eligible patients with early-stage AD in Great Britain as soon as possible. Eisai and Biogen will co-promote the drug in the region, with Eisai holding the Marketing Authorization and handling distribution.
Scientific Background
Apolipoprotein E is a protein crucial for fat metabolism in humans and plays a significant role in Alzheimer’s disease. Protofibrils, toxic aggregates of amyloid-beta, are considered a major contributor to the neuronal damage and cognitive decline observed in Alzheimer’s. These protofibrils not only promote the formation of insoluble amyloid plaques but also interfere with neuronal communication, leading to progressive cognitive impairment. By reducing protofibrils, lecanemab may mitigate neuronal damage and slow cognitive decline, potentially altering the course of the disease.
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