Leqembi, Formerly Lecanemab, Gets FDA Approval to Treat Alzheimer’s
Therapy should be available in US the week of Jan. 23 or before
Note: This story was updated Feb. 7, 2023, to correct the number of participants in the Study 201 (NCT01767311), which evaluated Leqembi in 856 people with early Alzheimer’s.
Lecanemab (BAN2401), Eisai and Biogen’s amyloid-targeted antibody therapy, has earned approval — under an accelerated approval pathway — from the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease.
The medication, to be sold in the country under the brand name Leqembi, should be initiated in patients with mild cognitive impairment or mild dementia, as stated in its label. To be eligible for treatment with Leqembi, patients must have confirmed beta-amyloid accumulation in the brain prior to treatment initiation.
“The FDA’s approval of LEQEMBI under the Accelerated Approval pathway is an important milestone in Eisai’s four decades of research in Alzheimer’s disease and reflects our continued commitment to alleviating the burden of Alzheimer’s disease for patients and their families,” said Haruo Naito, Eisai’s CEO, in a press release.
Therapy to cost $26,500 per year
According to Eisai, Leqembi should become available to patients in the U.S. the week of Jan. 23 or earlier at a launch price of $26,500 per year. This value may potentially be lower if the medication, which should initially be given by into-the-vein (intravenous) infusion at a dose of 10 mg/kg every two weeks, is administered less frequently once patients achieve a substantial reduction in the amount of beta-amyloid plaques under a maintenance regimen.
Eisai also has in place a special Patient Assistance Program meant to help financially disadvantaged patients gain access to Leqembi. Under this program, eligible uninsured and underinsured patients, including Medicare beneficiaries, who meet certain criteria, will have access to the therapy at no cost.
Additionally, Eisai is working with various payers, including the Centers for Medicare and Medicaid (CMS), TRICARE, the U.S. Veterans Health Administration and private health insurance companies to ensure appropriate beneficiaries have access to the therapy.
“The approval of LEQEMBI provides new hope to patients with Alzheimer’s disease. Patients at an early stage of the disease and their caregivers can now consider a new treatment option with their doctors. Our focus now is on the path forward, working alongside Eisai with the goal of making LEQEMBI available to patients who may benefit from this treatment as soon as possible,” said Christopher A. Viehbacher, Biogen’s president and CEO.
Virtually all Alzheimer’s cases are marked by the accumulation in the brain of beta-amyloid protein. The protein forms clumps that disrupt nerve cell function and ultimately lead to the death of these cells.
Co-developed by Eisai and Biogen, Leqembi is an antibody designed to target a toxic form of beta-amyloid that’s prone to clumping. It works to neutralize the protein and mark it for clearance by the immune system before it can aggregate.
“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” said Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.
The treatment earned breakthrough therapy status from the FDA in June 2021, and fast track designation last January. Both of these designations are intended to expedite a therapy’s development and regulatory review.
Shortly after earning its breakthrough status, Eisai began working on a rolling biologics license application for the treatment, under which the company was seeking accelerated approval for Leqembi.
The FDA’s accelerated approval pathway allows the regulatory agency to give conditional approval to therapies based on early clinical data indicating the treatment is likely to be effective. The treatment can then be marketed, but additional clinical data needs to be provided before it can achieve full approval.
In July, the FDA accepted the completed application and placed it under priority review, with an expected decision date of Jan. 6.
Clinical trial data on Leqembi
The regulatory application included data from a Phase 2b clinical trial called Study 201 (NCT01767311), which evaluated Leqembi in 856 people with early Alzheimer’s. It also used interim data from the Phase 3 Clarity AD trial (NCT03887455), which involved 1,795 people with early Alzheimer’s.
Findings from Study 201 demonstrated that Leqembi, given as an intravenous infusion twice monthly, led to a decrease in cognitive decline and prevented beta-amyloid accumulation in the brain relative to a placebo over 18 months.
An ongoing, open-label extension phase of that study aims to further probe the therapeutic benefits of Leqembi over several years.
In CLARITY AD, participants were similarly randomly assigned to receive infusions of Leqembi (10 mg/kg) or a placebo every two weeks for 18 months.
This trial’s main goal was to evaluate changes in dementia symptoms as assessed with the Clinical Dementia Rating-Sum Boxes (CDR-SB) scale.
At the time of the regulatory submission, Clarity AD efficacy data had not been made available. However, Biogen and Eisai published full study results from the trial late last year.
Data showed that Leqembi led to a significant 27% slowing of cognitive decline compared with the placebo.
Specifically, while those in the Leqembi group experienced a mean increase in CDR-SB scores of 1.21 points over 1.5 years, reflecting a worsening of dementia, those on placebo saw an even greater increase of 1.66 points.
Treatment also led to a significant and sustained reduction in amyloid plaques in the brain, and slowed disease progression in other clinical scales.
The findings were consistent across patient subgroups, regardless of disease stage, medication use, and genetic status.
Amyloid-related imaging abnormalities (ARIAs), such as swelling or bleeding in the brain, are known side effects of amyloid-targeted treatment.
In CLARITY AD, the rate of ARIA events was 21.3% among Leqembi-treated patients and 9.3% among those given the placebo — which the therapy’s developers noted as being expected rates.
The companies had previously stated that, should they be positive, final CLARITY AD data were expected to support full approval of Leqembi for Alzheimer’s. Eisai has now said it plans to rapidly submit an application to the FDA, based on published data from CLARITY AD, to request the therapy’s approval under a traditional pathway.
Meanwhile, another Phase 3 trial of Leqembi, called AHEAD 3-45 (NCT04468659), is underway. This study aims to evaluate the therapeutic effect of Leqembi in adults ages 55–80 who have preclinical Alzheimer’s. This condition is marked by elevated levels of amyloid in the brain, but no overt symptoms.
AHEAD 3-45 is recruiting up to 1,400 participants at more than 100 study sites worldwide. Top-line data for AHEAD 4-45 is expected in 2027.
Eisai also is working toward the therapy’s approval in Japan and China, and has plans underway for a European application.
The medicine’s prescribing information also includes a warning for ARIAs, which may not have overt symptoms, despite being potentially serious or life-threatening events. Enhanced patient monitoring for ARIAs is recommended during the first 14 weeks of treatment.