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Are there new safety concerns for Lecanemab?

Contributed by Joshua Grill, PhD and David Sultzer, MD

An article in ScienceInsider, a news outlet published by Science magazine, reports on an unpublished case of a person who died after treatment with the monoclonal antibody lecanemab.

There are two hallmarks of Alzheimer’s dementia: amyloid-beta protein deposits known as plaques, and tangles of a protein called tau, but several potential antibody therapies target just amyloid. KATERYNA KON/SCIENCE SOURCE

Lecanemab is a promising investigational treatment, seemingly poised for FDA approval as a disease-modifying treatment for Alzheimer’s disease. Topline results were announced in September that indicated lecanemab had been shown to slow progression of disease. The full data will be presented tomorrow at the Clinical Trials in Alzheimer’s Disease (CTAD) international conference.

The presentation should include efficacy as well as safety data for lecanemab. As noted previously and like all drugs, lecanemab has safety risks.

The new case will raise concerns about safety, though much information remains needed. While any death must be taken seriously, it is important to also note that there have now been thousands of people enrolled in trials of lecanemab and few such occurrences. The main risk associated with drugs like lecanemab is amyloid-related imaging abnormalities (ARIA), typically characterized by leakage or even bleeding in the brain as a byproduct of lowering amyloid levels. Though ARIA does not usually cause symptoms, it can have serious symptoms, such as headache, loss of balance, seizures, and even death.

According to the article in Science, the new case was a participant in a clinical trial of lecanemab who died shortly after beginning participation in an open-label extension study (a study in which all participants receive active medication, compared to the preceding double-blind study, in which some people receive active medication and some receive placebo). The participant was a 65-year-old woman who suffered a stroke and was taken to the emergency room, where she was treated with the stroke therapy tissue plasminogen activator (tPA). She apparently reacted immediately, experiencing bleeding in the brain that caused her death within a few days.

Learning more about this case, and the more complete data from the Phase 3 trial, will be key to instructing future research and appropriate clinical use of lecanemab, if it is approved. Alzheimer’s disease is a progressive disorder that robs patients of their cognitive abilities, functional independence, and ultimately their lives. Another important need, aside from better understanding the full risk profile of lecanemab and other drugs, is a better understanding of whether patients and families are willing to tolerate the associated risks.