U.S. health officials approved Friday aAn Alzheimer’s drug that moderately slows down the brain-robbing disease, albeit with a potential safety risk that patients and their doctors will need to consider carefully.
The drug, Leqembi, is the first to be convincingly shown to slow the memory and thinking decline that defines Alzheimer’s disease by targeting the underlying biology of the disease. The Food and Drug Administration has approved it for Alzheimer’s patients, especially those with mild or early-stage disease.
Leqembi, from Japanese company Eisai and its American partner Biogen, is a rare success in a field accustomed to failed experimental treatments for an incurable disease. The delay in cognitive decline caused by the drug is likely only a few months, but some experts say it can still significantly improve people’s lives.
“This drug is not a cure. It doesn’t stop people from getting worse, but it measurably slows the progression of the disease,” said Dr. Joy Snider, a neuroscientist at Washington University in St. Louis. “That could mean someone could have an extra six months to a year to drive.”
Snider pointed out that the drug, pronounced “leh-KEM-bee”, has drawbacks, including the need to infuse twice a month and possible side effects such as brain swelling.
FDA approval has come through an accelerated track that allows drugs to be introduced based on early results before they are confirmed to be of benefit to patients. The agency’s use of this short-cut approach is increasingly being watched by government watchdogs and congressional investigators.
Last week, a congressional report confirmed thisa similar drug for Alzheimer’s – also from Biogen and Eisai – was “full of irregularities”, including many undocumented meetings with employees of pharmaceutical companies.
The scrutiny of the new drug, known chemically as lekanemab, likely means most patients won’t start getting it for months as insurers decide whether and how to cover it.
The drug will cost around $26,500 for the typical annual cost of treatment. Eisai said the price reflects the drug’s benefits in terms of improving quality of life, reducing burdens on caregivers and other factors. The company has set its value at more than $37,000 a year, but said it has priced it lower to keep costs down for patients and insurers. An independent group that assesses the drug’s value recently concluded that the drug would need to be priced below $20,600 a year to be viable.
About 6 million people in the United States and many more worldwide suffer from Alzheimer’s disease, which progressively attacks areas of the brain needed for memory, reasoning, communication, and performing everyday tasks.
The FDA approval was based on one mid-stage study of 800 people with early signs of Alzheimer’s who were still able to live independently or with minimal assistance.
Eisai has since published the results of a larger study involving 1,800 patients that the FDA will review to confirm the drug’s benefits, paving the way for full approval later this year.
A larger study tracked patients’ performance on an 18-point scale that measures memory, judgment and other cognitive abilities. Physicians compile an assessment based on patient interviews and close contact. After 18 months, patients receiving Leqembi improved more slowly – less than half a point on the scale – than patients receiving a sham infusion. The delay was just over five months.
There is disagreement as to whether this difference translates into real benefits for patients, such as greater independence.
“Most patients won’t notice the difference,” said Dr. Matthew Schrag, a neuroscientist at Vanderbilt University. “It’s a really small effect and probably below the threshold of what we would call clinically significant.”
Schrag and some other researchers believe that a significant improvement would require at least a difference of one full point on an 18-point scale.
Leqembi works by removing a sticky brain protein called amyloid, which is one of the hallmarks of Alzheimer’s disease. But it’s not clear what exactly causes the disease. A number of other drugs targeting amyloid have failed and many researchers now believe that combination therapies will be needed.
Aduhelm, a similar drug, has been plagued by controversy over its effectiveness.
The FDA approved the drug in 2021 against the advice of the agency’s external experts. Doctors were hesitant to prescribe the drug, and insurers limited coverage.
The FDA did not consult the same panel of experts before approving Leqembi.
While there is “less drama” around the new drug, Schrag said many of the same concerns apply.
“Is this small, measurable benefit worth the enormous price and side effects that patients may experience?” he asked. “I have some pretty serious doubts.”
About 13% of the patients in the Eisai study had cerebral edema and 17% had minor brain bleeds, side effects seen with previous amyloid-targeting drugs. In most cases, these problems did not cause symptoms, which can include dizziness and vision problems.
In addition, several Leqembi users died while taking the drug, including two who were taking blood thinners. Eisai said the deaths could not be attributed to the drug. The FDA label warns doctors to be careful if they prescribe Leqembi to patients taking blood thinners.
Insurers are likely to cover the drug only for people like those in the company study – patients with mild symptoms and evidence of amyloid buildup. This usually requires expensive brain scans. A separate type of scan will be needed for periodic monitoring of brain swelling and bleeding.
A key issue in launching the drug will be the insurance decision made by Medicare, the federal health plan that covers 60 million seniors and other Americans. The agency severely limited Aduhelm’s reach, essentially destroying its US market and prompting Biogen to abandon its marketing plans for the drug.
Eisai executives said they had already spent months discussing their drug’s data with Medicare officials. Coverage is not expected until the FDA confirms the drug’s benefits, possibly later this year.
“Once we make the Medicare decision, we can really roll out the drug nationwide,” said Eisai US CEO Ivan Cheung.
Betsy Groves, 73, from Cambridge, Massachusetts, was diagnosed with Alzheimer’s disease in 2021. A former faculty member at Harvard’s teaching school noted that she had trouble remembering the names of some students and answering questions.
Her initial diagnosis, based on a cognitive function test, was later confirmed with a positive amyloid test.
Groves says she is “more than willing” to try Leqembi, despite the potential side effects and the need for infusions.
“For me, the moment this drug comes on the market – and I get my doctor’s approval – I’m going to take it,” Groves said.