Deaths in a clinical trial for Eisai’s Alzheimer’s disease drug lecanemab are once again being flagged, this time in a New England Journal of Medicine entry that highlights a potential risk for patients undergoing a certain type of emergency stroke treatment.
In a letter to the editor published in the NEJM Wednesday afternoon, researchers from the Northwestern University Feinberg School of Medicine detailed the death of a patient who was treated with lecanemab and a common clot-dissolving treatment for strokes, known as a tissue plasminogen activator, or t-PA, and suffered multiple brain bleeds.
The 65-year-old patient had a common genetic risk factor for Alzheimer’s and was in an early stage of cognitive decline. The patient previously participated in the phase 3 Clarity AD trial, and it’s not clear whether they received the treatment or placebo. But the patient went on to participate in the extension portion and received three doses of lecanemab.
Four days after receiving the final infusion, the person presented at the emergency room with stroke symptoms and t-PA was administered. Shortly after, the patient’s blood pressure spiked and the treatment stopped. A CT scan showed multiple brain bleeds and the patient later died.
The researchers conclude that 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.”
Continuing, the article suggests that “the findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with t-PA infusion in a patient with cerebrovascular amyloid who had received lecanemab.” In other words, the researchers believe that lecanemab could raise the risk of stroke and brain inflammation in patients with amyloid plaques in the brain who receive t-PA.
Eisai in its rebuttal agrees that the case “raises important management issues for patients with Alzheimer’s disease." Catastrophic brain bleeds have previously been reported after t-PA treatment in people who had amyloid presence in the brain, which is a known hallmark of Alzheimer’s; t-PA was considered the cause of death in this case. Eisai noted that another death in the lecanemab trial occurred in a patient with atrial fibrillation who was taking the anticoagulant apixaban, marketed by Bristol Myers Squibb as Eliquis.
“Although t-PA appears to be the proximate cause of death, this was an unusual case, and we understand why the authors want to highlight a potential concern,” Eisai said in the rebuttal. “These reports are consistent with the known increased risk of intracerebral hemorrhage in persons with [cerebral amyloid angiopathy].”
The company said the death occurred in an open-label extension of the Clarity AD trial, which is testing lecanemab’s ability to improve cognitive decline in Alzheimer’s patients. Eisai has been responding to several reports in recent weeks over deaths occurring in patients who took lecanemab, but this is the first time a medical journal has published an official research article on the events.
Lecanemab succeeded in the late-stage Clarity AD trial back in September, surprising an industry that has long gotten used to failures in Alzheimer’s. The FDA is due to rule on the drug's approval by Friday. Eisai worked with Biogen on lecanemab as well as the approved Alzheimer's med Aduhelm.