Side effects of the newly approved drug lecanemab (Leqembi) likely contributed to the death of a 65-year-old woman with Alzheimer’s disease, the authors of a new case study report. The findings highlight unresolved questions about how patients respond to this treatment, and how to best vet recipients, investigators say.
The patient was involved in a phase 3 study of the drug. She experienced stroke symptoms four days after a third infusion, and died several days later, investigators reported.
Upon autopsy, it was clear that the patient’s response to the drug, certain Alzheimer’s-related brain changes and anticoagulant treatment for stroke together may have led to hemorrhage and death, according to lead investigator Rudolph J. Castellani, MD, of the Northwestern University Feinberg School of Medicine in Chicago.
Improvements in clearing amyloid-beta from the brain were achieved, but they came at the expense of collateral injury to small blood vessels, which contributed to the adverse outcome, Castellani and colleagues reported.
Lecanemab prescribing considerations
The study team believes this outcome would not be an isolated occurrence. The side effects found in the case study, even if rarely symptomatic, can be devastating, according to M. Marsel Mesulam, MD, also of Northwestern. Screening for cerebrovascular disease and certain Alzheimer’s genetic risk factors may be essential in order to more more safely prescribe the drug, he said in a statement. And patients may also need to be told that anticoagulant treatment for stroke, if it occurs, may not be a safe option.
“The availability of lecanemab introduces a new phase in the treatment of Alzheimer’s disease,” but the benefits are “modest at the group level and unknowable in individual patients,” Mesulam added.
In fact, the drug and others in its class have long been associated with headache and amyloid-related imaging abnormalities (ARIA). Periodic MRI imaging is recommended to watch for asymptomatic ARIA in patients receiving the drug. Clinical trials of lecanemab have documented cases of ARIA. At least three deaths have occurred during the trials as well.
The question is whether individual patients receiving anti-amyloid-beta therapeutics can be adequately screened for factors that may increase their risk of adverse outcomes, Castellani added.
Better biomarkers for assessing patients’ suitability for treatment are needed, the authors concluded.
The case study was published in the Journal of Alzheimer’s Disease. An earlier study was published in the New England Journal of Medicine. Science magazine has also reported on this case.
Related studies:
FDA approves new drug Leqembi to treat early Alzheimer’s disease
VHA to cover new Alzheimer’s drug Leqembi, despite CMS’s restraint
