The U.S. Food and Drug Administration (FDA) has approved lecanemab, the second-ever treatment for Alzheimer’s disease, which aims to target the cause of the condition and slow cognitive decline. Researchers applaud the decision, but excitement is tempered by patient deaths and reports that the FDA acted improperly in approving the first drug of its kind last year.
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By slowing disease progression when taken in the early stages of Alzheimer’s disease, lecanemab will allow people “to have more time to participate in daily life and live independently,” says Joanne Pike, President and executive director of the Alzheimer’s Association in Washington DC, in a statement.
Lecanemab, sold under the brand name Leqembi, is the first Alzheimer’s drug to slow cognitive decline in a robust clinical trial and the second to be approved in less than two years. It is manufactured by biopharmaceutical companies Eisai in Tokyo, Japan and Biogen in Cambridge, Massachusetts. The drug, a monoclonal antibody, is infused intravenously into patients, enters the brain and removes the amyloid plaques thought to cause cognitive impairment and dementia in Alzheimer’s.
“The results offer hope to patients and families, but they are also an important step in developing successful ways to modify and prevent clinical onset of the disease,” said Eric Reiman, executive director of the Banner Alzheimer’s Institute in Phoenix, Arizona.
Lecanemab was approved under the agency’s “accelerated approval pathway,” which is reserved for therapies for diseases for which there are few treatments; no data from phase III clinical trials are required either. However, researchers are hopeful about Biogen and Eisai’s Phase III data, which were released in November 20221. This study, conducted on about 1,800 people with early-stage Alzheimer’s, found that the antibody slowed cognitive decline by 27% over 18 months of treatment.
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The FDA’s decision does not take into account the Phase III study — Biogen and Eisai filed for accelerated approval based on Phase II data that they submitted before the latest study results were announced. The phase II study found that lecanemab reduced plaques in the brains of 856 patients, but did not assess whether this affected the patients’ cognitive abilities. This is the same pathway used to approve its predecessor, aducanumab, a similar antibody also made by Biogen and Eisai.
It’s unclear what impact this 27 percent effect will have on the lives of people with Alzheimer’s — or if this effect lasts after 18 months. It could mean, Reiman says, “an extra 6 months to recognize a loved one’s face or do a worthwhile activity.” But that will require future research, he says. In the meantime, the FDA says lecanemab should only be used for people with mild cognitive impairment — the same cohort used in the clinical trials.
Diana Zuckerman, president of the National Center for Health Research, a nonprofit in Washington DC, isn’t sure the benefit is worth the risk. “You’re dealing with people with mild cognitive impairment who are functioning, and you’re putting them at risk,” she says, both in terms of their health and their finances. Eisai says a year of lecanemab will cost $26,500 in the United States.
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in the last few months, Science and STAT messages reported on three people who had been enrolled in the phase III study of lecanemab and then died during the extended phase of the study, in which patients receiving placebo can ask to be given the drug. They died of complications including cerebral hemorrhage and seizures. According to these reports, researchers believe the patients may have died from a variety of conditions known as amyloid-related imaging abnormalities (ARIA). They suspect the antibody weakened blood vessels in the brain as it attacked the amyloid plaques lining them. All of the patients were taking anticoagulant medications at the time, which may have made the bleeding worse.
Eisai has said it is inappropriate to draw conclusions based on individual cases and has reported the deaths to the FDA as required. Still, FDA approval requires that lecanemab include a warning about ARIA and that physicians monitor the condition, which is rarely serious or life-threatening.
The controversy surrounding aducanumab, which the FDA granted accelerated approval on June 7, 2021, is casting a shadow over lecanemab. Many researchers thought that aducanumab, also known by the brand name Aduhelm, did not show a strong signal of cognitive decline. The FDA’s Scientific Advisory Panel recommended against approval of the antibody by a vote of 8-1, and three members of the panel resigned after the FDA approved it anyway. The FDA did not hold a public advisory meeting prior to the approval of lecanemab.
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Since aducanumab’s approval, Biogen and the FDA have faced further scrutiny that has limited the treatment’s adoption. A congressional investigation released last month found that the agency broke its own rules by improperly guiding Biogen through the aducanumab approval process. The report said the process was “riddled with irregularities” and raised “serious concerns about FDA protocol errors and Biogen’s disregard for efficacy,” but did not penalize the FDA or the companies.
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The US Center for Medicare and Medicaid Services (CMS) has declined to cover aducanumab under state insurance plans unless a person is enrolled in a clinical trial, leaving most patients over $28,000 for one year to pay for treatment. CMS — and several clinics that refused to prescribe the drug — cited its questionable effectiveness, drawing the ire of stakeholders who say it should be readily available.
Despite the controversy, Reiman hopes lecanemab’s success will open the door to faster approvals in the future. He’s currently working with pharmaceutical company Eli Lilly to test its similar monoclonal antibody, donanemab, in a phase III study that he says is promising so far. The FDA is expected to make a decision on donanemab approval in the coming weeks.