By Deena Beasley
(Reuters) – Emergency treatment with a blood clot buster called tissue plasminogen activator for a patient who had a stroke while being treated with the experimental Alzheimer’s drug lecanemab led to a fatal cascade of brain hemorrhage and burst blood vessels, an autopsy analysis published on Wednesday suggests.
The death of the a 65-year old woman after receiving three doses of the Eisai Co Ltd Alzheimer’s drug was first reported in November.
The Japanese drugmaker at the time said that available safety information indicated lecanemab therapy was not associated with an increased risk of death overall.
The intravenously administered clot-clearing medicine tissue plasminogen activator (t-PA) is the indicated hospital treatment for acute ischemic stroke.
Lecanemab, developed by Eisai and Biogen Inc, is an antibody designed to remove sticky deposits of a protein called amyloid beta from the brains of early-stage Alzheimer’s patients. Trial results have shown that the drug reduced the rate of cognitive decline by 27% compared to a placebo.
Researchers suggest that the combination may have played a role in the death.
“The extensive number and variation in sizes of the cerebral hemorrhages in this patient would be unusual as a complication of t-PA solely related to cerebrovascular amyloid,” researchers from Northwestern University Feinberg School of Medicine in Chicago said in correspondence published in the New England Journal of Medicine.
The successful trial also found that lecanemab was associated with a dangerous type of brain swelling in nearly 13% of patients. Some also experienced bleeding in the brain, with five suffering macrohemorrhages and 14% suffering microhemorrhages.
“We agree that this case raises important management issues for patients with Alzheimer’s disease,” Eisai researchers said in a response to the Northwestern analysis.
They noted that the deceased patient carried two copies of a gene known to increase the risk of developing Alzheimer’s and of brain swelling from treatment with an anti-amyloid therapy.
The autopsy showed extensive brain hemorrhaging, amyloid deposits in the brain, Alzheimer’s disease neuropathologic changes, and inflammation involving amyloid deposits within the blood-vessel walls, the analysis said.
A second brain hemorrhage death was reported last year of an 87-year-old man who was being treated with lecanemab and the widely-used blood thinner Eliquis.
The U.S. Food and Drug Administration is slated to decide by Friday whether to approve lecanemab under its accelerated review program, which requires proof that a drug can impact a biomarker associated with a disease, such as reduction of amyloid beta in the brain.
(Reporting By Deena Beasley; Editing by Bill Berkrot)
