By Ernie Mundell HealthDay Reporter
(HealthDay)
THURSDAY, Jan. 5, 2023 (HealthDay News) — Lecanemab: It’s an experimental medication that is been shown in trials to slow cognitive decline in individuals with Alzheimer’s disease.
It is also up for accelerated approval by the U.S. Food and Drug Administration, with a choice expected by Jan. 6.
Nonetheless, the drug has also been linked to 2 deaths from brain bleeds amongst individuals who’ve used it in trials, so safety concerns could threaten any approval.
If approved, the drug — made by Japanese pharmaceutical company Eisai — would follow the controversial drug Aduhelm to grow to be only the second medication ever approved to slow Alzheimer’s disease.
Not every patient would stand to profit from lecanemab, stressed the Cleveland Clinic’s Dr. Babak Tousi. He led the portion of the clinical trial that was conducted on the Cleveland Clinic, in Ohio.
“The trial was designed for patients in the sooner stage of Alzheimer’s disease, individuals with mild cognitive impairment or early stage of dementia,” Tousi noted. “If this medication gets approval, it is going to probably be for individuals who have early stage of disease, with no to minimal assistance needed for activities of day by day living.”
The outcomes of the 18-month trial, which involved about 1,800 patients, gained wide attention once they were published Dec. 1 within the Latest England Journal of Medicine, Tousi noted.
Within the trial, early-stage Alzheimer’s patients who took lecanemab showed a 27% reduction of their mental decline in comparison with patients within the placebo arm of the trial. The drug’s users also showed less evidence of amyloid protein plaques of their brain in comparison with non-users.
Amyloid buildup within the brain has long been an indicator of Alzheimer’s disease.
“Lecanemab clearly did what it was designed to do — it removed amyloid plaque,” said Tousi, who heads the Clinical Trials Program on the Cleveland Clinic Center for Brain Health.
“Lecanemab identifies this amyloid and helps the body do away with it,” he explained. “The outcomes demonstrated all of the downstream effects we hoped would occur when it comes to reduction of biomarkers and fewer clinical decline on several functional and cognitive measures. So, this difference will likely translate to an extended period of independent living for patients.”
Two patient deaths raise questions
Still, the deaths of two patients enrolled within the trial solid a cloud on these hopeful findings. Each died from brain hemorrhages that appear linked to using lecanemab.
In a single case, a 65-year-old woman with early-stage Alzheimer’s died from an enormous brain bleed that some researchers link to lecanemab, in line with a report published Nov. 27 in Science Insider.
The lady suffered a stroke, in addition to a form of brain swelling and bleeding that’s been previously seen with such antibodies, the report noted.
ER doctors at Northwestern University Medical Center in Chicago treated the girl with a typical but powerful clot-busting drug, tissue-plasminogen activator (t-PA). She immediately had substantial bleeding throughout her brain’s outer layer.
“As soon as they put it in her, it was like her body was on fire,” her husband told Science Insider. “She was screaming, and it took like eight people to carry her down. It was horrific.”
The lady died a couple of days later, the case report said.
The death follows that of an 80-year-old man who was participating in lecanemab’s phase 3 clinical trial. His death was linked to a possible interaction between the experimental drug and a blood thinner called apixaban (Eliquis).
Rudolph Castellani, a Northwestern neuropathologist who autopsied the girl, determined that she had amyloid deposits surrounding lots of her brain’s blood vessels.
The lady had been receiving biweekly infusions of lecanemab, which appears to have inflamed and weakened her blood vessels, Castellani said. These vessels then burst when exposed to the clot-buster, something that may occur even in conventional stroke cases.
“It was a one-two punch,” Castellani told Science Insider. “There’s zero doubt in my mind that it is a treatment-caused illness and death. If the patient hadn’t been on lecanemab, she can be alive today.”
While Eisai declined to comment on the girl’s case, the corporate did issue a statement saying that “All of the available safety information indicates that lecanemab therapy is just not related to an increased risk of death overall or from any specific cause.”
The lady may need received either lecanemab or a placebo throughout the 18-month trial, but she was definitely given the drug throughout the month preceding her death. She’d opted to receive it as a part of an open-label extension of the clinical trial.
The lady and the person each had widespread cerebral amyloid angiopathy (CAA), a condition during which amyloid deposits regularly replace the sleek muscle of blood vessel partitions.
Nearly half of Alzheimer’s patients have CAA, and lots of also suffer from heart ailments which might be normally treated with blood thinners, the report noted.
Experts explained to Science Insider that in these kinds of patients, stripping the amyloid away — as drugs like lecanemab are supposed to do — could weaken the blood vessels and make them vulnerable to bleeds if exposed to blood thinners or clot busters.
More details on the girl’s case — including autopsy results — were released Wednesday within the Latest England Journal of Medicine by doctors at Northwestern Medicine in Chicago. The autopsy confirmed extensive brain bleeding and amyloid deposits inside many blood vessels.
The Northwestern team believes that exposure to t-PA triggered burst blood vessels throughout the patient’s brain, causing death.
“The extensive number and variation in sizes of the cerebral hemorrhages on this patient can be unusual as a complication of t-PA solely related to cerebrovascular amyloid,” they wrote, but prior use of lecanemab can have tipped the balance, triggering the hemorrhages.
In a journal response to the article Drs. Marwan Sabbagh and Christopher H. van Dyck said they “agree that this case raises vital management issues for patients with Alzheimer’s disease.”
But aspects apart from the patients’ use of lecanemab might have been at play, they identified. In the girl’s case, an prolonged period of very hypertension might have been a contributing factor. In the person’s case, a drug he was taking to counter atrial fibrillation may need played a job within the hemorrhaging.
Sabbagh and van Dyck also noted that amyloid deposits inside blood vessels have been seen before in individuals who died after getting t-PA.
Besides the 2 fatal cases, the clinical trial also showed that 2.8% of participants who took the drug had a symptomatic side effect called ARIA-E, which involves swelling within the brain. ARIA-E was not seen amongst any participants who got the placebo.
Nonetheless, for the hundreds of thousands of Americans affected by Alzheimer’s, any helpful drug might be welcome.
The anticipation constructing around lecanemab follows the controversial June approval of an identical Alzheimer’s drug, Aduhelm, regardless that studies didn’t prove the treatment worked and showed serious safety risks.
After Medicare limited its coverage of Aduhelm, citing risks and unclear profit, the expensive drug was essentially sidelined.
Like Aduhelm, lecanemab — given via infusion every two weeks — is a monoclonal antibody that targets a protein, amyloid, that tends to clump within the brains of individuals with Alzheimer’s. Years of research have uncovered precious little evidence that clearing these plaques actually helps with memory and pondering problems. Earlier this month, one other anti-amyloid monoclonal antibody, gantenerumab, failed to point out any profit.
For his part, Tousi stressed that lecanemab is not going to produce a dramatic turnaround within the cognitive health of individuals with Alzheimer’s disease.
“It is just not that you simply take this medication and your memory gets higher,” he said. “It’s a more recent concept for a lot of patients. It is just not treating the symptoms but it surely slows down the decline. … It’s a small profit but continues to be a profit. The findings are promising after we don’t have every other treatments available.”
Visit the U.S. National Institute on Aging for more on Alzheimer’s.
SOURCES: Babak Tousi, MD, head, clinical trials program, Cleveland Clinic Center for Brain Health, Ohio; Latest England Journal of Medicine, Jan. 5, 2023 and Dec.1, 2022; Science Insider, Nov. 27, 2022
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