Safety data on Alzheimer's drug lecanemab limited, cardiologists call for more research

NEW DELHI: Cardiologists are advocating for additional research on the drug lecanemab that can add to the limited safety data, currently used for decision-making before initiating treatment of Alzheimer’s disease, according to a viewpoint article published in the Journal of the American Medical Association (JAMA).

Initially granted an “accelerated approval” in January 2023, lecanemab received full approval from the US Food and Drug Administration (FDA) for the treatment of mild cognitive impairment (MCI) or early dementia due to Alzheimer’s disease on 6 July last year.

MCI, an early stage of memory or cognition loss characterised by low confidence in executing daily activities, can prevail for a few years before advancing to early Alzheimer’s disease — a progressive neurodegenerative disease that destroys memory and, eventually, the ability to carry out the simplest, everyday tasks.

Lecanemab is an anti-amyloid monoclonal antibody medication that targets the deposits or plaques of amyloid beta proteins in the brain, typically associated with Alzheimer’s disease.

A study published in The New England Journal of Medicine in January 2023, showed the drug to slow down the progression of the disability by 27 percent over 18 months of the drug being administered. Close to 1,800 participants were enrolled — 898 were assigned to receive lecanemab and 897 to receive a placebo.

Points out safety concerns

However, in the latest article, the researchers have pointed to major safety concerns from using the drug arising out of bleeding in the brain, or cerebral macrohaemorrhage. It is one of a range of amyloid-related imaging abnormalities (ARIA), which refer to abnormalities seen in the imaging of the brains of Alzheimer’s disease patients.

While mostly asymptomatic and rare, the ARIA cases of cerebral macrohaemorrhage are “troubling” because of its potential for death and disability, said the researchers from Harvard Medical School and Boston Medical Center, US, in the study.

“The risk was higher in patients on anticoagulation (or blood thinners),” said author Darae Ko, a cardiologist and member of the faculty of medicine at the Harvard Medical School.

In the JAMA article, the authors noted that in approving lecanemab, the FDA did not advise regarding the risk of concurrent anticoagulation therapy, and that persons with cerebral amyloid angiopathy (amyloid deposits on the blood vessels of the brain) and those currently prescribed anticoagulants were recommended against being candidates for lecanemab because the risk of bleeding outweighed the potential benefit.

The authors anticipated that in patients being treated with anti-amyloid medication, it would be particularly challenging to make critical clinical decisions with regard to three common acute clinical conditions — stroke, heart attacks and blood vessel blockages, owing to limited safety data on lecanemab, which they described as “an important advance in the treatment of Alzheimer’s”.

“To meet this challenge,” the authors wrote, “there is a pressing need to create multidisciplinary treatment teams for Alzheimer’s Disease, develop shared decision-making models for advanced care planning, and produce the empiric data needed to guide treatment decisions.”