WASHINGTON — U.S. health officials on Friday approved a closely watched Alzheimer’s drug that’s been shown to modestly slow the early stages of the brain-robbing disease, albeit with potential safety risks that doctors and patients will have to carefully weigh.
The drug, Leqembi, is the first that’s been convincingly shown to slow the decline in memory and thinking that defines Alzheimer’s by targeting the disease's underlying biology. The Food and Drug Administration approved it specifically for patients with mild or early cases of dementia.
Leqembi, from Japan's Eisai and its U.S. partner Biogen, is a rare success in a field accustomed to failed experimental treatments for the incurable condition. The delay in cognitive decline brought about by the drug likely amounts to just several months, but some experts say it could still meaningfully improve people's lives.
“This drug is not a cure. It doesn’t stop people from getting worse, but it does measurably slow the progression of the disease,” said Dr. Joy Snider, a neurologist at Washington University in St. Louis. “That might mean someone could have an extra six months to a year of being able to drive.”
Snider stressed that the medicine, pronounced “leh-KEM-bee,” comes with downsides, including the need for twice-a-month infusions and possible side effects like brain swelling and bleeding.
Approval came via FDA's accelerated pathway, which allows drugs to launch based on early results, before they're confirmed to benefit patients. The agency's use of that shortcut has come under increasing scrutiny from government watchdogs and congressional investigators.
Last week, a congressional report found that FDA's approval of a similar Alzheimer's drug called Aduhelm — also from Biogen and Eisai — was “rife with irregularities,” including a number of meetings with drug company staffers that went undocumented.
Scrutiny of the new drug, known chemically as lecanemab, will likely mean most patients won’t start receiving it for months, as insurers decide whether to cover it and for whom.
The drug will cost $26,500 for a typical year’s worth of treatment. Eisai said that price reflects the drug’s benefit in terms of improved quality of life, reduced burdens for caregivers and other factors. The company pegged its overall value at $37,000 per year, but said it priced the drug lower to reduce costs for patients and insurers. An independent group that assesses drug value recently said the drug would have to be priced below $20,600 to be cost-effective.
Some 6 million people in the U.S. and many more worldwide have Alzheimer’s, which gradually attacks areas of the brain needed for memory, reasoning, communication and daily tasks.
The FDA's approval was based on one mid-stage study in 850 people with early symptoms of Alzheimer's who also tested positive for a type of brain plaque that is a hallmark of the disease.
Since then, Eisai has published the results of a larger 1,800-patient study that the FDA is expected to soon review to confirm the drug's benefit, setting up a decision on full approval later this year.
The larger study tracked patients’ results on an 18-point scale that measures memory, judgment and other cognitive abilities. Doctors compile the rating from interviews with the patient and a close contact. After 18 months, patients receiving Leqembi declined more slowly — a difference of less than half a point on the scale — than patients who received a dummy infusion. The delay amounted to just over five months.
There is little consensus on whether that difference translates into real benefits for patients, such as greater independence.
“Most patients won’t notice the difference,” said Dr. Matthew Schrag, a neurology researcher at Vanderbilt University. “This is really quite a small effect and probably below the threshold of what we’d call clinically significant.”
Schrag and some other researchers believe a meaningful improvement would require at least a difference of one full point on the 18-point scale.
Leqembi works by clearing a sticky brain protein called amyloid that’s a key indicator of Alzheimer’s. But it’s not clear exactly what causes the disease. A string of other amyloid-targeting drugs have failed and many researchers now think combination treatments will be needed.
Aduhelm, the similar drug, was marred by controversy over its effectiveness.
The FDA approved that drug in 2021 against the advice of the agency's own outside experts. Doctors hesitated to prescribe the drug and insurers restricted coverage.
The FDA did not consult the same expert panel before approving Leqembi.
Rep. Rosa DeLauro of Connecticut — a frequent FDA critic — said in a statement Friday that she was “deeply concerned that FDA chose to forego" a panel meeting on the drug.
Schrag said many of the same concerns apply to both drugs.
“Is this slight, measurable benefit worth the hefty price tag and the side effects patients may experience?” he asked. “I have pretty serious doubts.”
About 13% of patients in Eisai’s study had swelling of the brain and 17% had small brain bleeds, side effects seen with earlier amyloid-targeting medications. In most cases those problems didn’t cause symptoms, which can include dizziness and vision problems.
Also, several Leqembi users died while taking the drug, including two who were on blood-thinning medications. Eisai has said the deaths can’t be attributed to the drug. The FDA label warns doctors to use caution if they prescribe Leqembi to patients on blood thinners.
Insurers are likely to only cover the drug for people like those in the company study — patients with mild dementia and confirmation of amyloid buildup. That typically requires expensive brain scans or a spinal fluid test. Doctors will need to perform a different type of scan to periodically check for brain swelling and bleeding.
A key question in the drug’s rollout will be insurance coverage by Medicare, the federal health plan that covers 60 million seniors and other Americans. The agency severely restricted coverage of Aduhelm, essentially wiping out its U.S. market and prompting Biogen to abandon marketing plans for the drug.
Eisai executives said they have already spent months discussing their drug's data with Medicare officials. Coverage isn't expected until after the FDA confirms the drug's benefit, expected later this year.
“Once we have a Medicare decision, then we can truly launch the drug across the country," said Eisai's U.S. CEO, Ivan Cheung.
Betsy Groves, 73, was diagnosed with Alzheimer’s in 2021. A former lecturer at Harvard’s graduate school of education, she noticed she was having trouble remembering some student names and answering questions.
Her initial diagnosis, based on a cognitive examination, was later confirmed by a positive test for amyloid.
Groves, of Cambridge, Massachusetts, says she is “more than willing” to try Leqembi, despite potential side effects and the need for infusions.
“For me, the minute that drug comes on the market — and I get my doctor’s approval — I’m going to take it,” Groves said.
Some 6 million people in the U.S. and many more worldwide have Alzheimer’s, which gradually attacks areas of the brain needed for memory, reasoning, communication and daily tasks.
The FDA's approval was based on one mid-stage study in 800 people with early signs of Alzheimer's who were still able to live independently or with minimal assistance.
Since then, Eisai has published the results of a larger 1,800-patient study that the FDA will review to confirm the drug's benefit, paving the way for full approval later this year.
The larger study tracked patients’ results on an 18-point scale that measures memory, judgment and other cognitive abilities. Doctors compile the rating from interviews with the patient and a close contact. After 18 months, patients receiving Leqembi declined more slowly — a difference of less than half a point on the scale — than patients who received a dummy infusion. The delay amounted to just over five months.
There is little consensus on whether that difference translates into real benefits for patients, such as greater independence.
“Most patients won’t notice the difference,” said Dr. Matthew Schrag, a neurology researcher at Vanderbilt University. “This is really quite a small effect and probably below the threshold of what we’d call clinically significant.”
Schrag and some other researchers believe a meaningful improvement would require at least a difference of one full point on the 18-point scale.
Leqembi works by clearing a sticky brain protein called amyloid that’s one hallmark of Alzheimer’s. But it’s not clear exactly what causes the disease. A string of other amyloid-targeting drugs have failed and many researchers now think combination treatments will be needed.
Aduhelm, the similar drug, was marred by controversy over its effectiveness.
The FDA approved that drug in 2021 against the advice of the agency's own outside experts. Doctors hesitated to prescribe the drug and insurers restricted coverage.
The FDA did not consult the same expert panel before approving Leqembi.
While there's “less drama,” surrounding the new drug, Schrag said many of the same concerns apply.
“Is this slight, measurable benefit worth the hefty price tag and the side effects patients may experience?” he asked. “I have pretty serious doubts.”
About 13% of patients in Eisai’s study had swelling of the brain and 17% had small brain bleeds, side effects seen with earlier amyloid-targeting medications. In most cases those problems didn’t cause symptoms, which can include dizziness and vision problems.
Also, several Leqembi users died while taking the drug, including two who were on blood-thinning medications. Eisai has said the deaths can’t be attributed to the drug. The FDA label warns doctors to use caution if they prescribe Leqembi to patients on blood thinners.
Insurers are likely to only cover the drug for people like those in the company study — patients with mild symptoms and confirmation of amyloid buildup. That typically requires expensive brain scans. A separate type of scan will be needed to periodically monitor for brain swelling and bleeding.
A key question in the drug’s rollout will be the coverage decision by Medicare, the federal health plan that covers 60 million seniors and other Americans. The agency severely restricted coverage of Aduhelm, essentially wiping out its U.S. market and prompting Biogen to abandon marketing plans for the drug.
Eisai executives said they have already spent months discussing their drug's data with Medicare officials. Coverage isn't expected until after the FDA confirms the drug's benefit, likely later this year.
“Once we have a Medicare decision, then we can truly launch the drug across the country," said Eisai's U.S. CEO, Ivan Cheung.
Betsy Groves, 73, of Cambridge, Massachusetts, was diagnosed with Alzheimer’s in 2021. A former lecturer at Harvard’s school of education, she noticed she was having trouble remembering some student names and answering questions.
Her initial diagnosis, based on a cognitive examination, was later confirmed by a positive test for amyloid.
Groves says she is “more than willing” to try Leqembi, despite potential side effects and the need for infusions.
“For me, the minute that drug comes on the market — and I get my doctor’s approval — I’m going to take it,” Groves said.
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AP Medical Writer Lauran Neergaard contributed to this report
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