An experimental treatment for Alzheimer’s disease may pose a life-threatening risk of brain bleeding for certain patients, an investigative report out this week suggests. The paper, published Monday in the journal Science, details the case of a 65-year-old woman who died from massive hemorrhaging that could have arisen from taking a common blood thinner while on the experimental drug. The incident is believed to be the second similar death linked to the treatment, which will be reviewed for approval by the Food and Drug Administration early next year.
The treatment is known as lecanemab and is being jointly developed by the pharmaceutical companies Biogen and Eisai. It’s a lab-made antibody intended to go after amyloid beta, a protein that’s believed to play a pivotal role in Alzheimer’s disease. In people with Alzheimer’s, hardy, toxic clumps of amyloid known as plaques form throughout the brain, damaging it over time. The drug primarily tries to break down amyloid deposits that haven’t yet turned into these plaques, which should in theory stop or at least slow down the progression of Alzheimer’s symptoms.
Earlier this September, the companies announced their latest Phase III trial results of lecanemab. Compared to those on placebo, patients taking lecanemab seemed to experience a slower rate of cognitive decline, while also having lower measured levels of amyloid. The findings appeared to be the first time that any anti-amyloid drug had shown clearly significant, if likely modest, benefits in large-scale clinical research. But even this apparent success has now been tempered by these reports of fatal complications linked to the drug.
As part of their investigation, Science interviewed the woman’s family and doctors. They were also given access to an unpublished case report written by her doctors and asked outside experts to evaluate the findings.
According to the report, the woman had been part of the original 18-month trial of lecanemab, though likely as part of the placebo group. Afterward, she was given the option to start taking lecanemab and agreed to do so. Sometime later, the woman had a stroke, which prompted a trip to the emergency room at the Northwestern University Medical Center in Chicago. She was then given the blood thinner tissue plasminogen activator (tPA), a common stroke treatment meant to restore blocked blood flow. Immediately after, however, her condition rapidly worsened as she developed severe brain bleeding, and she was soon placed on a ventilator. With no apparent hope of recovery, her family disconnected her life support a few days later.
“It was a one-two punch,” Rudolph Castellani, a Northwestern neuropathologist and Alzheimer’s expert who conducted an autopsy of the woman at her husband’s request, told Science. “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.”
The report follows a similar death reported in late October by STAT News, which involved a man in his 80s who also seemingly developed fatal brain bleeding while taking a combination of lecanemab and a blood thinner. In an adverse event report, Eisai conceded that the treatment may have played a part in the man’s death, but it has since argued that the death was unrelated, and the incident reportedly remains under investigation.
Human trials of these anti-amyloid drugs have shown that they can increase the risk of brain bleeding in people who take them, but never to the life-threatening extent seen in these cases. Experts interviewed by Science argue that the drug’s effect on amyloid deposits near blood vessels may have weakened them to the point where the introduction of a blood thinner could have then caused massive ruptures. If that’s true, then these reports could prompt a serious reevaluation of the drug’s expected risks and benefits by the FDA, especially since many older patients at risk of Alzheimer’s have to take blood thinners to treat or manage other health conditions, like stroke. At the very least, it could lead to explicit warning labels attached to these drugs moving forward.
Most previous drugs of this class have outright failed to pass major clinical tests, including a candidate that recently failed in trials. Last year, the FDA approved the first drug of this kind, Aduhelm, which was also developed by Biogen and Eisai. But that decision was immediately marred by controversy, since the trial data supporting its approval was mixed at best, and the FDA went against the express recommendations of its outside advisory committee in doing so. Aduhelm remains on the U.S. market for now but will not be routinely covered by Medicare until its makers can provide further compelling data for its effectiveness (in March, Eisai signed over any remaining responsibility for Aduhelm to Biogen).
As for lecanemab, Eisai is expected to present more detailed findings from its Phase III trial later this week at an Alzheimer’s research conference. The FDA is scheduled to make a decision concerning its approval by January next year.