The FDA, which gave the drug a bullish review in documents released Wednesday, is expected to grant Leqembi regular approval in early July. During the meeting Friday, Teresa Buracchio, acting director of the agency’s Office of Neuroscience, acknowledged an ongoing debate about whether Leqembi produces a large enough benefit for patients.
But Buracchio made it clear that the FDA believes the benefit is “clinically meaningful” because it extends the patient’s time in the earlier, less severe phase of the disease. Leqembi does not reverse damage caused by Alzheimer’s, but it does slow the progression of the disease by about five to six months, the data indicate.
Even as the drug moves forward, it seems unlikely that controversy over its safety and cost will abate. And a controversial Medicare plan Imposing restrictions on coverage fuels fierce disagreements among politicians, medical experts and advocates for people with Alzheimer’s.
Tensions were on display during the public hearing of Friday’s meeting of the Advisory Committee on Drugs on the Peripheral and Central Nervous System.
Patricia Bencivenga, special projects coordinator for PharmedOut, a project at Georgetown University that criticizes the pharmaceutical industry’s marketing practices, said Leqembi should not be given full approval. “It doesn’t work,” she said, adding that the drug poses significant safety concerns and can make dementia worse.
But several other speakers said slowing the progression of the disease would give desperate patients valuable time to take part in the lives of their families and communities.
“We just want the chance for a little more time to be the people we are today, tomorrow,” said Doreen Monks, 70, who was forced to retire as a nurse in 2016 after being diagnosed with early-onset Alzheimer’s .
About 6.5 million Americans have Alzheimer’s, which is the fifth leading cause of death for people 65 and older. Leqembi and similar therapies being developed reduce amyloid plaques in the brain, a hallmark of the disease. The medicines are monoclonal antibodies – man-made proteins that can bind to specific targets in the body.
Leqembi was approved by the FDA on an accelerated basis in January based on preliminary data showing its amyloid-lowering effect. That approval required a confirmatory study confirming that the drug benefited patients by slowing the disease.
The drug, which is made by Eisai, a Japanese pharmaceutical company, and Biogen, based in Cambridge, Mass., is administered intravenously twice a month. The price is 26,500 dollars a year. The medicine has been developed for people with mild cognitive impairment or early dementia caused by Alzheimer’s.
Traditional FDA approval would pave the way for a broad launch of Leqembi and some form of coverage by Medicare, the federal health program for the elderly and disabled. The Centers for Medicare and Medicaid Services, which runs Medicare, recently said it would cover Leqembi — and other Alzheimer’s drugs receiving traditional approval — for patients who are willing to take part in data registries designed to track the effects of the treatments in the real world.
Leqembi, which is also called lecanemab, has the potential to cause serious side effects, including swelling of the brain and bleeding; three deaths from cerebral hemorrhages occurred in the extended part of the trial. The FDA said the patients had a condition called cerebral amyloid angiopathy, which is the buildup of amyloid in small arteries and capillaries in the brain. The condition can be difficult to detect by imaging.
But in a discussion about whether the FDA should strengthen the label for the drug, committee members said they were reluctant to urge the agency to exclude patients who may have the condition. Their opinions were more divided on whether the drug should be withheld from patients on anticoagulants, which according to some indications increases the risk of complications.
Some committee members said people on blood thinners should not take the drug, but others said there was not enough data to justify blocking the treatment for such a large number of older people.
Under the current label for the drug, the agency warns of potential complications and suggests increased monitoring.
Anti-amyloid drugs, which have failed after failures in trials before signs of potential effectiveness emerged in recent years, have ravaged the Alzheimer’s field for years.
Another antibody drug, Aduhelm, received accelerated approval from the FDA in 2021, but failed in the market due to intense skepticism over conflicting data and sharp coverage limits imposed by Medicare. Another drug in the same group, donanemab by Eli Lilly, has shown promising results and may receive regular FDA approval later this year or early next year.
Eisai has estimated that the number of people with early Alzheimer’s who will be eligible for Leqembi will be around 100,000 three years after the drug received traditional approval. This estimate, which some analysts say is conservative, reflects the significant time required to adopt new screening and diagnostic technologies to confirm the accumulation of amyloid beta in the brain, the company has said.
By 2022, Medicare said it would not cover any Alzheimer’s antibody drug approved by accelerated approval unless a patient is enrolled in a CMS-approved clinical trial. It has billed its recent decision to provide coverage for certain patients taking fully approved drugs — provided they participate in an ongoing registry — as a way to gather much-needed information about the treatments.
Some experts have supported Medicare’s position, arguing that there are outstanding questions about safety and efficacy that need to be addressed. But advocates such as the Alzheimer’s Association and others have condemned that plan, saying requiring registries for coverage would delay access to the treatment and discriminate against people who don’t have access to academic medical centers, which are best positioned to participate in data-gathering efforts.
The rise of Leqembi is also fueling the debate on Capitol Hill. Sen. Bernie Sanders (I-Vt.), chairman of the Senate Health Committee, recently urged the Biden administration to take steps to lower the cost of the drug.
“We cannot allow pharmaceutical companies to bankrupt Medicare and our federal government in the process,” Sanders said.
But Rep. Anna G. Eshoo, the ranking Democrat on the House subcommittee on health, and Rep. Nanette Barragán — both California Democrats — expressed concern in the other direction: that the Medicare coverage plan could make it difficult for anyone who needs Leqembi to get it.
“There must be clarity and transparency about the standards of coverage for FDA-approved treatments for terminal illnesses with unmet medical need,” the lawmakers wrote to CMS Administrator Chiquita Brooks-LaSure. “Please do not let CMS’s requirement for additional evidence generation be a barrier to patient care.”