Alzheimer's Drug Leqembi Gains FDA Panel's Support for Full Approval

Alzheimer's Drug Leqembi Gains FDA Panel's Support for Full Approval
Vials and packaging for Eisai's medication Leqembi. (Eisai via AP)
Mimi Nguyen Ly

A group of independent advisers to the U.S. Food and Drug Administration (FDA) have voted to support regulatory approval of the Alzheimer's drug Leqembi, also known by its generic name lecanemab, despite concerns surrounding three deaths during clinical trials.

The six members on the Peripheral and Central Nervous System Drugs Advisory Committee on Friday all voted in favor of the FDA granting full approval to Leqembi to treat Alzheimer's, saying the drug shows a clinical benefit in patients with mild cognitive impairment or early dementia caused by Alzheimer's.

Alzheimer's is a progressive brain disease that causes a range of cognitive impairments, including memory loss. Later in the disease, a person may lose the ability to have conversations, respond to the environment, and carry out daily tasks. The disease affects 6 million Americans, according to the Alzheimer's Association.

The FDA doesn't have to follow the panel's recommendation but it generally does. It is expected to make a final decision on whether to grant Leqembi full approval by July 6. If approved, Medicare payment for the treatment is expected to expand.

Accelerated Approval

Leqembi was developed by Japanese pharmaceutical company Eisai in partnership with U.S. biotechnology company Biogen. It is a monoclonal antibody that's administered intravenously twice a month and costs $26,500 a year.
It won accelerated FDA approval in January, making it the first such FDA-approved drug that targets part of the pathophysiology of Alzheimer’s and that can improve cognitive function. Specifically, Leqembi removes plaques of a sticky protein called amyloid from the brain, one of the characteristics of Alzheimer's.

Another class of the drug, aducanumab, sold under the brand name Aduhelm and approved by the FDA in 2021, also removes amyloid plaques from the brain but does not result in cognitive improvement.

The FDA's accelerated approval program allows early access to drugs for serious conditions where there is an unmet medical need, and there are laboratory or biological results that suggest the drug would benefit patients.

Drugs approved via the accelerated pathway can technically be withdrawn by the FDA if their benefits aren't confirmed, though regulators rarely take that step. Gaining full approval allows medications to stay on the market indefinitely.

Study Shows Benefits

A large study supported by Eisai showed that lecanemab benefited patients, the panel determined on Friday.
The study, published in November 2022 in the New England Journal of Medicine, showed that lecanemab reduced the rate of cognitive decline by 27 percent over 18 months.

The double-blind phase 3 clinical trial was carried out on 1795 patients in the early stages of Alzheimer’s disease—with 898 assigned to receive lecanemab and 897 to receive a placebo.

Lecanemab delayed patients’ worsening by about five months over the course of the study, Eisai’s Dr. Michael Irizarry previously told The Associated Press. Patients taking the drug were also 31 percent less likely to advance to the next stage of the disease during the study.

“That translates to more time in earlier stages” when people function better, Irizarry said.

"I believe the benefit versus risk are beneficial, acceptable, and in line with this class of therapeutics, especially considering the burden of the disease and the progressive nature of the disease," panel member Dr. Tanya Simuni, professor of neurology at Northwestern University Feinberg School of Medicine, said on Friday.

"Overall, it demonstrated clearly that this is an effective treatment in the population as it was defined," Dr. Robert Alexander, committee chair and an Alzheimer's expert at the Banner Alzheimer's Institute, said on Friday. He added that he thought the study "clearly demonstrated a clinical benefit," calling the results "robust."

Side Effects and Deaths

However, the study also showed there lecanemab presented some serious side effects for some participants, including brain swelling, as well as bleeding—also referred to as micro-hemorrhages. They reported symptoms of headaches, visual disturbances, and confusion.

Three patients taking Leqembi died during the study.

One of the patients, before receiving lecanemab, had suffered a stroke and received a blood thinner. A separate patient, a woman, suffered stroke symptoms after starting on lecanemab, and later suffered seizures before her death a few days later. Doctors found massive bleeding in the woman's brain.

A third individual who was on lecanemab was also treated for acute ischemic stroke with tissue plasminogen activator, and died afterwards from multiple hemorrhages in the brain.

FDA reviewers said it was unclear whether lecanemab played a role in their deaths due to other underlying factors such as the blood-thinning medications that can increase the risk of bleeding.

FDA Panel Offers Advice on Certain Patients

The FDA asked the advisory panel to offer recommendations on the use of lecanemab in certain patient groups. This included people taking blood-thinning medications; people who have APOE4, a gene variant that increases the risk of Alzheimer's; and people with cerebral amyloid angiopathy (CAA), a rare condition marked by buildups of amyloid in the walls of arteries in the brain that can cause bleeding.

Regarding those with the APOE4 gene, panel members generally said the risks were balanced by the benefits, but they advised the FDA to recommend genetic testing for the gene in Leqembi's prescribing label.

For those on blood thinners, some members expressed concerns, while others said patients should be made aware of the risks of bleeding but still be provided the option to take the drug.

Members said they wouldn't recommend excluding patients with CAA, which can be difficult to diagnose, but that Leqembi should be limited in patients with the most severe cases of CAA due to more risk of brain hemorrhages.

Medicare Coverage

Currently, under accelerated approval, the Centers for Medicare and Medicaid Services (CMS) limits payment of the drug to patients enrolled in clinical trials.

But no such trials are underway for Leqembi, resulting in negligible sales. Patients who have received the drug since its accelerated approval have mainly had to pay out of pocket.

CMS Administrator Chiquita Brooks-LaSure has said the program will immediately begin covering the drug if it gets full FDA approval.

But last week she announced an extra condition, even after CMS coverage begins, for patients to receive payment for the treatment—they will need to be enrolled in a federal health agency database, known as a registry, to track the drug's safety and effectiveness. However, CMS has yet to release details of its plan.

Stephanie Zhang, Reuters, and The Associated Press contributed to this report.