In a large study, the experimental drug lecanemab was able to slow, but not stop, the progression of Alzheimer’s disease. I think it will be Others have questions.
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Semir Bingol/Getty Images
In a large study, the experimental drug lecanemab was able to slow, but not stop, the progression of Alzheimer’s disease. I think it will be Others have questions.
Semir Bingol/Getty Images
A drug that offers little benefit to people with Alzheimer’s disease has created a sensation among doctors treating the disease.
The drug, a monoclonal antibody called lecanemab, was released last week in Alzheimer’s disease clinical trial meeting in San Francisco.
At the meeting, researchers study About 1,800 people in the early stages of Alzheimer’s disease. The person who took lecanemab during her 18 months had a 27% reduction in her memory and thinking skills.
The study was paid for by pharmaceutical company Eisai, which is developing lecanemab in collaboration with US company Biogen.
“There was a sense of elation, like this was a milestone in the fight against Alzheimer’s disease,” he said. Dr. Eric Lymanexecutive director of the Banner Alzheimer’s Institute in Phoenix.
“I’m so excited to finally have something,” he says. Dr. Leisa SperlingHe directs the Alzheimer’s Research and Treatment Center at Brigham and Women’s Hospital in Boston. “It’s not a cure, but it’s really a new beginning.”
A scientific event has become a “celebration,” he says. Maria Carrillo, Chief Scientific Officer of the Alzheimer’s Association. “The data are undeniably positive.”
However, other scientists say the drug’s benefits are modest and the risks, such as brain swelling and bleeding, are significant.
“This is a very small effect size for a drug that has several side effects, including brain shrinkage,” he said. Dr. Madhav Thambiseti, a neurologist at the National Institute on Aging, part of the National Institutes of Health. Also, the evidence that it slows disease progression is “not convincing,” he said, adding that his view is his own, not that of the NIH.
long winding road
Lecanemab’s apparent success comes after decades of frustration with other similar drugs aimed at slowing or stopping the progression of Alzheimer’s disease.
Lecanemab, like many other drugs, contains a lab-made monoclonal antibody designed to clear a substance called beta-amyloid from the brain. Beta-amyloid is a protein that tends to form clumps in the brains of people with Alzheimer’s disease, ultimately resulting in the sticky plaques that characterize Alzheimer’s disease.
But a long list of antibodies targeting beta-amyloid failed to slow the decline in memory and thinking associated with Alzheimer’s disease. amyloid hypothesis – The idea that amyloid is the primary cause of brain cell loss, leading to poor memory and thinking.
Only one amyloid antibody has been approved by the Food and Drug Administration and is controversial.
Aducanumab, marketed under the name Aduhelm, was conditionally approved by the FDA in 2021, but evidence was conflicting about whether it would benefit patients. The move came after a panel of experts advising the authorities voted against the approval.
Since then, the Federal Medicare Program has decided to cover Aduhelm treatment only for patients enrolled in clinical trials. As a result of that decision and the widespread negative publicity regarding this drug, most patients do not receive it.
Solid results, with warnings
The results for lecanemab are much more pronounced.
“It impacted a range of cognitive and functional measures that are important for families and family caregivers,” says Reiman. “It would be surprising if it didn’t get full approval” from the FDA.
The agency plans to consider conditional approval in early 2023 and full approval later this year. If approved, lecanemab will likely be limited to people with early-stage Alzheimer’s disease, who make up about two million of her six million people with the disease.
However, safety concerns remain about lecanemab and most other drugs that clear amyloid from the brain. The most common concern is a condition known as ARIA, or amyloid-related imaging abnormalities.
Two types of ARIA are commonly seen in brain scans of people taking amyloid drugs. One is swollen and the other is bleeding.
In a study of lecanemab, more than 12% of people who took the drug had swelling and more than 17% had bleeding.
“This sounds very dramatic. You have swelling and bleeding in your brain,” he says. Dr. Sharon Cohenmedical director of the Toronto Memory Program in Canada, one of the sites testing lecanemab. But the reality, she says, is not so alarming.
“What we’ve learned over time is that very few individuals have symptoms,” Cohen said.
However, in rare cases, patients can experience brain damage or even death. So far, two deaths have been attributed to lecanemab, although both patients had other conditions that may have contributed to the results.
The risk of ARIA appears to be higher in people who take blood thinners or who carry a gene that causes very high levels of amyloid in the brain. There will be patients who don’t have it,” she says.
Lecanemab and other drugs that clear amyloid have other side effects that are more mysterious. It seems to shrink the brain.
It concerns scientists including Thambiseti.
“Brain shrinkage represents disease progression,” he says. “What worries me a little bit is that these drugs may be exacerbating the degenerative process.”
Alzheimer’s disease itself causes the brain to shrink. This is a sign that neurons are dying. So Tambiseti hoped that Alzheimer’s drugs would limit rather than accelerate contractions.
That’s why I did Dr. David Nopman of the Mayo Clinic. “It’s going in the wrong direction,” he said at a panel at the Alzheimer’s Conference.
Thambisetti would like Eisai to release more information about the changes in brain volume that occurred during the study of lecanemab.
“It is incumbent on drug developers and researchers to try to prove that these changes are benign and do not represent a serious adverse event,” he says.
Other scientists point out that drugs for diseases like cancer often have serious side effects.
“I think there are many [Alzheimer’s] Patients and their doctors are willing to take some risks,” Sperling said. Our job is to minimize risk.
