A 65-year-old woman who was receiving a promising experimental treatment to slow the cognitive decline caused by her early Alzheimer’s disease recently died from a massive brain hemorrhage that some researchers link to the drug. The clinical trial death, described in an unpublished case report Science has obtained, is the second thought to be associated with the antibody called lecanemab. The newly disclosed fatality intensifies questions about its safety and how widely lecanemab should be prescribed if ultimately approved by regulators.
The woman, who received infusions of the antibody as part of the trial, suffered a stroke and a type of swelling and bleeding previously seen with such antibodies, which bind to and remove forms of amyloid-beta, a protein widely theorized to cause Alzheimer’s. After the stroke was diagnosed in an emergency room at Northwestern University Medical Center in Chicago, she was given a common intervention, the powerful blood-clot busting medication tissue plasminogen activator (tPA). Substantial bleeding immediately followed throughout her brain’s outer layer immediately followed, and the woman died a few days later, according to the case report.
Rudolph Castellani, a Northwestern neuropathologist who studies Alzheimer’s and conducted an autopsy at the request of the patient’s husband, called the case “very dramatic.” The report, co-authored by Castellani, concluded that the woman, like the other person whose death was linked to lecanemab, had amyloid deposits surrounding many of her brain’s blood vessels. This pre-existing condition, found in both Alzheimer’s patients and to a lesser degree in the general population, frequently goes undetected other than by autopsy. It likely contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels. The vessels apparently burst when exposed to tPA—known to cause brain bleeds even in some conventional stroke cases.
“It was a one-two punch,” Castellani says. “There’s zero doubt in my mind that this is a treatment-caused illness and death. If the patient hadn’t been on lecanemab she would be alive today.” (Castellani says his comments reflect personal views and were not reviewed or approved by Northwestern. The patient’s husband told Science he authorized Castellani to speak publicly about his wife’s case. Science agreed to withhold both names to protect the family’s privacy.)
Castellani, his co-authors, and other researchers say the newly disclosed death suggests that tPA and perhaps other, less potent blood thinners pose safety considerations for Alzheimer’s patients receiving the antiamyloid antibody drugs, including lecanemab. The 30-page consent form for trial participants, obtained by Science, carries this warning about blood thinners: “You may continue with these medications, but you and the investigator should discuss the risk of bleeding since medications which prevent clots and [lecanemab] are both associated with a slight risk of bleeding in the brain.” It does not address tPA directly.
The woman’s husband says the events surrounding her death were fully disclosed to Great Lakes Clinical Trials, the Chicago-based contract research organization that administered lecanemab to his wife as part of the antibody’s international, multicenter study. He attended a postmortem meeting with Great Lakes principal investigator and psychiatrist Jeffrey Ross, and a Northwestern physician who had participated in his wife’s stroke care. According to the husband, Ross said during the meeting that he had shared details of the case with Eisai Co., the Japanese company that originally developed lecanemab with the Swedish firm BioArctic and sponsored the trial with its U.S. biotech partner Biogen. Ross did not respond to requests for comment.
Eisai declined to comment on the woman’s case, including…
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