The Food and Drug Administration has, for the second time, approved a medicine meant to slow the progression of Alzheimer’s disease.
In granting a so-called accelerated approval, the agency on Friday cleared the way to a new and sought-after option for the millions of people living with mild forms of the disease in the U.S. The medicine, which is known scientifically as lecanemab but will be sold under the brand name Leqembi, was developed through a partnership between the Japan-based pharmaceutical company Eisai and Biogen.
Eisai said that, for an average patient, Leqembi will cost $26,500 per year. While the company defended the price as below the drug’s value to society, it’s likely to draw scrutiny given the potential for Leqembi to be used widely. It’s also above the range cited by one influential nonprofit as potentially cost-effective.
The FDA’s decision comes three months after results from a large trial showed treatment with Leqembi slowed patients’ physical and mental decline by 27% compared to a placebo over an 18-month period.
The findings were the first clear-cut success for a drug of Leqembi’s type in late-stage clinical testing. Still, experts remain torn about the magnitude of the drug's benefit, especially in light of its potential safety risks.
While the FDA noted those results in its announcement Friday, Leqembi’s approval was based primarily on an earlier study that, despite complicated and much-debated results, initially suggested Eisai and Biogen’s drug had an effect on the disease.
The study enrolled more than 800 patients with early Alzheimer’s and tested different doses of Leqembi. It found that, at multiple times across an 18-month treatment period, patients treated with the highest dose had slower cognitive decline compared to those in the placebo group, as measured by a scale created by Eisai.
Importantly for the FDA’s decision-making, Leqembi worked as it was designed to — breaking up aggregates of a toxic brain protein called amyloid beta. In 2021, the FDA similarly cleared another Biogen and Eisai drug, Aduhelm, for its ability to bind to and eliminate these protein clusters, making it the first therapy approved in the U.S. for the treatment of Alzheimer’s itself rather than symptoms of the disease.
Yet, amyloid and its role in Alzheimer’s remain a controversial topic among researchers and physicians. Until Aduhelm, every closely watched experimental medicine targeting amyloid had failed in key clinical trials. And the data supporting Aduhelm was conflicting, leading to widespread doubts among doctors that it could actually help patients.
As with Aduhelm before it, the FDA’s approval of Leqembi is conditional. But unlike with Aduhelm, Eisai and Biogen already have the needed confirmatory results in hand and plan to use those more recent findings to secure a full clearance of their drug in the coming months.
In its statement, the FDA said it anticipates receiving that data “soon.”
Leqembi’s launch on the market will be closely tracked. Like other amyloid-targeting therapies, the safety of Leqembi has become a focal point. In the larger trial, around a fifth of patients given the drug experienced swelling or small bleeds in their brains. Reporting from Stat News and Science has also detailed how there have been at least three patient deaths that appear linked to Leqembi and the brain bleeding it causes.
“Blood on the brain is not good,” Constantine Lyketsos, director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins Medicine, said in an interview late last year.
“When we’re talking about a drug that … will potentially be given to hundreds of thousands, if not millions, of people, then the risks, the numbers of people who will have these hemorrhages become very large,” added Lyketsos, who has consulted for Eisai and other drug companies.
This week, the New England Journal of Medicine published a case report detailing one of the deaths, which involved a 65-year-old patient given Leqembi during an extension portion of the larger study.
According to the report's authors, the patient experienced a stroke four days after their last Leqembi infusion. Healthcare providers administered a treatment designed to break down blood clots, but the patient’s blood pressure unexpectedly spiked. Brain scans later showed swelling and many “extensive” bleeds.
The authors concluded that the number and variety of these bleeds would be an “unusual” complication of the stroke treatment alone. They noted, too, how the patient carried two copies of a gene that researchers believe increases a patient’s likelihood of developing Alzheimer’s as well as having side effects from amyloid-targeting drugs.
In a response also published in NEJM this week, two of the researchers that led the large study of Leqembi agreed the patient's death “raises important management issues” for Alzheimer's patients, particularly those with two copies of that gene.
Eisai and Biogen have said that, in most cases, patients with these brain side effects showed no symptoms. The relative few who did often experienced headaches, visual disturbances and confusion.
The drug’s labeling includes a warning for amyloid-related imaging abnormalities, which is associated with the brain swelling and small bleeds. The label also cautions of the risk of infusion-related reactions.
For the two companies, Leqembi’s approval offers a shot at redemption after obstacles tripped up the launch of Aduhelm.
Once expected by analysts to be a blockbuster product, Aduhelm has generated only several million dollars since coming to market. The drug’s annual price tag — initially set at $56,000 before Biogen halved it in late 2021 — drew widespread criticism. And alongside the costs, healthcare and insurance providers took issue with Aduhelm’s trial results, too.
One payer with a particularly large influence is Medicare, the government insurance program that serves older adults and would therefore cover many Alzheimer’s patients. In April, the agency strictly limited coverage of Aduhelm and drugs like it that are cleared under an accelerated approval.
The agency’s policy now applies to Leqembi as well. But, if the drug were to secure a full approval as Eisai and Biogen hope it will in the coming months, that could remove many of the obstacles which limited Aduhelm.
A successful launch would be especially valuable to Biogen, which has seen most of its core products decline in revenue over the past couple years due to increased competition.
Leqembi, too, may soon face competition. Another anti-amyloid Alzheimer’s drug, Eli Lilly’s donanemab, is currently under FDA review, and could secure an accelerated approval by February. Its application was based on promising findings from a mid-stage study, but Lilly expects to have results from a roughly 1,800-person trial in April.