Eisai Co., Ltd. and Biogen Inc. announced today that the Ministry of Health and Prevention in the United Arab Emirates (UAE) has approved humanized anti-soluble aggregated amyloid-beta (Aβ) monoclonal antibody “LEQEMBI®” (lecanemab) for the treatment of Alzheimer’s disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease (collectively referred to as early AD), the population in which treatment was initiated in clinical trials.

LEQEMBI selectively binds to soluble Aβ aggregates (protofibrils*), as well as insoluble Aβ aggregates (fibrils) which are a major component of Aβ plaques, thereby reducing both Aβ protofibrils and Aβ plaques in the brain. LEQEMBI is the first approved treatment shown to reduce the rate of disease progression and to slow cognitive and functional decline through this mechanism. LEQEMBI is also approved in the U.S., Japan, China, South Korea, Hong Kong, and Israel, and is being marketed in the U.S., Japan, and China.

LEQEMBI’s approval is based on the large global Phase 3 Clarity AD study. In the Clarity AD study, LEQEMBI met its primary endpoint and all key secondary endpoints with statistically significant results.(1),(2) In the UAE, it is reported that 4.09% of those over 60 years old have dementia.(3) AD is considered the most common cause of dementia, typically accounting for 60-70% of cases.(4)

Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority. Biogen will commercialize LEQEMBI in the UAE.

* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.(5) Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.(6)
 
 Lecanemab (LEQEMBI®)

Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).

LEQEMBI’s FDA approval was based on Phase 3 data from Eisai’s, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results.1,2 The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with LEQEMBI reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with LEQEMBI and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo. The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the LEQEMBI group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001). The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the LEQEMBI group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.

LEQEMBI is approved in the U.S., Japan, China, South Korea, Hong Kong and Israel for the treatment of MCI due to AD and mild AD dementia. Eisai has also submitted applications for approval of LEQEMBI in 11 countries and regions. A supplemental Biologics License Application (sBLA) for intravenous maintenance dosing was submitted to the U.S. Food and Drug Administration (FDA) in March 2024, which was accepted in June 2024. The rolling submission of a Biologics License Application (BLA) for maintenance dosing of a subcutaneous injection formulation, which is being developed to enhance convenience for patients, was initiated in the U.S. under Fast Track status in May 2024.

Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.