Report shares new details about death possibly linked to experimental Alzheimer’s drug

CNN
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The death of a participant in a clinical trial of an antibody treatment for Alzheimer’s disease, which is currently under review by the United States Food and Drug Administration, may be linked to the experimental drug, according to a new report.

The research letter, published Wednesday in the New England Journal of Medicine, shares details about what happened to the participant in the open-label extension phase of the lecanemab trial.

In an open-label extension, there is no placebo arm; instead, all participants receive the drug in question because an earlier part of the trial showed so much potential.

In this case, a 65-year-old man who was in the early stages of Alzheimer’s disease was taken to the emergency room of a Chicago-area hospital within 30 minutes of the first signs of a stroke, the report says. . Doctors at Northwestern University Feinberg School of Medicine learned that the patient had received lecanemab infusions four days previously.

This patient is not the only one to die during open arm extension. Health publication Stat reported an investigator told them about the death of another participant who had bleeding in the brain that may have been drug-related. In this case, drugmaker Eisai pointed out other possible factors.

Lecanemab is intended to slow the progression of Alzheimer’s disease. In November, the company published a study showing that it slowed the progression of cognitive impairment 27% drop compared to a placebo. It also reduced levels of amyloid – a protein that is one of the hallmarks of Alzheimer’s disease – and had positive effects on cognition and the ability to perform daily tasks compared to a placebo.

The research also showed that around 2.8% of trial participants who took the drug had a symptomatic side effect called ARIA-E, which involves swelling of the brain. None of the participants who received a placebo had any.

The new report says the medical team at the hospital gave the patient a common medicine to break up blood clots that could cause a stroke, called a bolus of t-PA. Nothing in the patient’s medical history suggested he would have a problem with this drug. But within an hour of starting treatment, their blood pressure skyrocketed, so doctors stopped the infusion.

A CT scan showed significant bleeding in the brain.

Doctors then administered a drug that can control the bleeding, but the patient became very agitated and developed communication problems. The patient also had frequent nonconvulsive seizures.

The medical team was able to treat the seizures, but the person’s condition did not improve.

After three days in the hospital, the person received a tube in his trachea to help him breathe. Even with this and other supportive care, the patient died.

An autopsy showed the patient had severe brain bleeds and amyloid deposits in numerous blood vessels in his brain that likely contributed to the hemorrhage, the report said.

According to the report, the blood vessels in the patient’s brain must have burst after being exposed to t-PA, a drug against blood clots.

“The large number and variation in size of cerebral hemorrhages in this patient would be unusual as a complication of t-PA solely related to cerebrovascular amyloid,” the report states. But the combination of the anti-clot drug with lecanemab may have led to the brain hemorrhages.

Northwestern Medicine declined CNN’s request to interview the authors of the new report, but said in a statement that it was “an effort to provide relevant data to the medical and scientific community.”

Eisai said he didn’t have an official response due to patient confidentiality.

The company and Northwestern Medicine highlighted a response published alongside the new report from clinicians and researchers involved in lecanemab clinical trials.

Drs. Marwan Sabbagh and Christopher H. van Dyck wrote in this response that they “agree that this case raises significant management issues for patients with Alzheimer’s disease.”

This is an “unusual case, and we understand why the authors want to highlight a potential problem,” they said.

Their response also pointed to other potential factors in the deaths of the two trial participants.

In this case, the brain bleed could have been linked to a time after the stroke when the patient’s blood pressure was unusually high, they said. And the other trial participant was taking medication for atrial fibrillation which may have been a contributing factor.

The doctors also write in the response that other patients who received t-PA died with these amyloid deposits in the blood vessels of the brain.

Dr. Sharon Cohen, a behavioral neurologist who works with Alzheimer’s patients at the Toronto Memory Program and an investigator in the lecanemab trial, says it’s been difficult to develop a treatment for Alzheimer’s disease .

Cohen said doctors have known for years that almost any drug in this class can have a side effect of ARIA, which stands for amyloid-related imaging abnormalities.

The drug’s safety “seems very acceptable,” she said. “This is within the range of adverse events we would expect and seems very reasonable for this patient population.”

The bleeding rate in the trial is considered very low and most of the microhemorrhages seen in the trial were asymptomatic, she said.

In the case of the patient in the new report, Cohen believes the death was likely related to the blood clot drug, but said the combination of that drug and lecanemab “gives us pause.”

If the FDA approves the treatment, there may be some discretion in terms of patient choice and what the prescribing physician thinks is best for someone taking blood thinners or who has other risk factors for heart disease. bleeding, she said.

Overall, lecanemab exceeded our expectations in many ways, she said, “because we’ve never seen such positive results in an Alzheimer’s disease modification trial until now.” .