FDA Approves New Maintenance Dosing for Lecanemab to Treat Early-Stage Alzheimer Disease

The FDA approved Eisai's supplemental biologics license application (sBLA) yesterday for the intravenous (IV) maintenance dosing of lecanemab (Leqembi), an anti-amyloid antibody that helps slow the pace of cognitive decline, to treat patients with early-stage Alzheimer disease (AD) once every 4 weeks.¹

With this approval, patients who've received 10 mg/kg of lecanemab biweekly for 18 months may now transition to a maintenance dosing regimen of 10 mg/kg once every 4 weeks. The sBLA was based on the modeling of observed data from the phase 2 Study 201 trial (NCT01767311) and its open-label extension (OLE), along with data from the Clarity AD study (Study 301; NCT03887455) and its OLE.

Modeling simulations predicted that transitioning patients to once-every-4-week maintenance dosing after 18 months of biweekly treatment will maintain the therapy's clinical and biomarker benefits. Also, ongoing treatment with lecanemab was shown to slow disease progression and prolong therapy benefits to help patients preserve their cognitive and functional abilities.

Lecanemab was originally approved in January 2023 through the accelerated pathway to treat patients with mild cognitive impairment or dementia based on data from the phase 2b Study 201 trial.² This followed the controversial approval of aducanumab (Aduhelm; Biogen), which the FDA granted an accelerated approval in 2021 despite the lack of a recommendation from the FDA advisory committee.

Before being discontinued in January 2024, aducanumab was the first new AD therapy in nearly 2 decades.³ However, it was met with intense scrutiny and debate due to the small amount of evidence proving that the drug's reduction of amyloid improves patients' memory and cognitive issues.² In response, CMS announced in 2022 that it would restrict Medicare coverage for all approved monoclonal antibodies directed against amyloid to treat patients with AD participating in qualifying clinical trials.

In July 2023, lecanemab received full approval after Clarity AD, a global, confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized trial, verified the therapy’s clinical benefit⁴; this made it the first amyloid beta-directed antibody with full approval.

Clarity AD evaluated 1795 patients with AD who had mild cognitive impairment or dementia and a confirmed presence of amyloid beta pathology. They were randomized 1:1 to receive either a placebo or the treatment (10 mg/kg) once every 2 weeks. Compared with placebo, lecanemab reduced cognitive and functional decline by 27% at 18 months. It also slowed disease progression by 24%, cognitive function decline by 26%, and decline of daily living activities by 37%.

“This confirmatory study verified that it [lecanemab] is a safe and effective treatment for patients with Alzheimer’s disease,” Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a statement.

After it received accelerated approval, CMS said it would consider covering lecanemab. Following the FDA’s traditional approval of lecanemab, CMS subsequently granted broader Medicare coverage of the treatment.

“With the FDA’s decision, CMS will cover this medication broadly while continuing to gather data that will help us understand how the drug works,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “This is welcome news for the millions of people in this country and their families who are affected by this debilitating disease.”

References

1. FDA approves Leqembi (Lecanemab-IRMB) IV maintenance dosing for the treatment of early Alzheimer’s disease. News release. FDA; January 26, 2025. Accessed January 27, 2025. https://media-us.eisai.com/2025-01-26-FDA-Approves-LEQEMBI-R-lecanemab-irmb-IV-Maintenance-Dosing-for-the-Treatment-of-Early-Alzheimers-Disease
2. Joszt L. FDA approves lecanemab to treat early Alzheimer disease. January 6, 2023. Accessed January 27, 2025. https://www.ajmc.com/view/fda-approves-lecanemab-to-treat-early-alzheimer-disease
3. Joszt L. Biogen abandons aducanumab, pivots focus to lecanemab for Alzheimer disease. January 31, 2024. Accessed January 27, 2025. https://www.ajmc.com/view/biogen-abandons-aducanumab-pivots-focus-to-lecanemab-for-alzheimer-disease
4. Joszt L. FDA grants full approval for Alzheimer drug lecanemab. July 6, 2023. Accessed January 27, 2025. https://www.ajmc.com/view/fda-grants-full-approval-for-alzheimer-drug-lecanemab