FDA Approves Monthly IV Maintenance Dosing of Lecanemab for Adults with Early Alzheimer Dementia: A First in Long-Term Disease Management

The FDA today announced its approval of monthly intravenous (IV) dosing of lecanemab (Lequembi) to treat early-stage Alzheimer disease (AD) with confirmed presence of ß-amyloid, according to Eisai Pharma, the drug's sponsor.1

For individuals who have completed the 18-month induction phase of biweekly lecanemab infusions, the maintenance regimen calls for a monthly IV dose to maintain a concentration of the drug that sustains clearance of highly toxic protofibrils, precursors to the ß-amyloid plaque that induction treatment has cleared from the brain, according to the company news release. The once-monthly dosing is projected to reduce the burden of ongoing treatment for adults with Alzheimer disease as well as their care partners, Eisai said.1

Lecanemab was granted traditional approval by the FDA in January 2023 under the agency's accelerated approval pathway based on findings from the phase 2 study known as the 201 study, then later granted full approval based on data from the phase 3 Clarity AD study. The sBLA for monthly dosing was supported by modeling of observed data from Study 201, Clarity AD, and both trials' open-label extension (OLE) studies.1

The monoclonal antibody, jointly developed by Eisai and Biogen, was created to address 2 processes underlying the cognitive and functional decline seen in Alzheimer dementia. Lecanemab clears protofibrils, believed to contribute to neuronal injury and to be the most toxic form of ß-amyloid, and also "rapidly clears plaque," according to the news release. These disease-modifying mechanisms separate lecanemab and a second anti-amyloid antibody, donenemab, from previous medications for the disease that address symptoms only.1

Pivotal Trial

Clarity AD, the foundational trial for the FDA approval, evaluated 1795 patients with Alzheimer disease who had mild cognitive impairment or mild dementia and a confirmed presence of ß-amyloid pathology. They were randomized 1:1 to receive either a placebo or the treatment (10 mg/kg) once every 2 weeks. Published in the New England Journal of Medicine,2 study findings showed that lecanemab met its primary end point of change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, with treated patients demonstrating a statistically significant 27% reduction in cognitive and functional decline vs placebo.2 The biweekly IV infusion also slowed disease progression by 24%, decline in activities of daily living by 37%, and decline of cognitive function by 26%. Secondary endpoint data specifically showed change in amyloid PET centiloids (difference in least squares [LS], –50.12; P <.001) and Alzheimer’s Disease Assessment Scale-Cognitive 14 (LS difference, –1.442; P = .001) relative to placebo over the 18-month period.2

Open label extension. Three-year data from the open-label extension of Clarity AD, presented at the 2024 Alzheimer's Association International Conference, demonstrated Over 3 years of treatment across main study and the OLE, lecanemab reduced cognitive decline on the CDR-SB by –0.95 points compared with the expected decline observed in the Alzheimer’s Disease Neuroimaging Initiative study. A change from 0.5 to 1.0 on key CDR score domains reflects the difference between “slight impairment and loss of independence,” according to a separate Eisai press release.3

Label warnings. Prescribing information for lecanemab including a warning for amyloid-related imaging abnormalities, or ARIA, which are know to occur with antibodies in this drug class. In Clarity AD, symptomatic ARIA occurred in 3% of lecanemab-treated participants; serious symptoms were reported in 0.7%. Clinical symptoms of ARIA resolved in 79% of observed cases during observation. Overall, ARIA, including asymptomatic radiographic events, was observed in 21%of lecanemab-treated patients compared to 9% with placebo.2

1. FDA approves Leqembi (lecanemab) IV maintenance dosoing for the treatment of early Alzheimer's diease. News relase. Eisai US. January 26, 2025. Accessed January 26, 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. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948
3. New clinical data demonstrate three years of continuous treatment with dual-acting Lequembi (lecanemab-irmb) continues to significantly benefit early Alzheimer's disease patients presented at AAIC 2024. News release. Eisai Co, Ltd. July 31, 2024. Accessed January 26, 2025.