Eisai and Biogen have announced that the United Arab Emirates (UAE) Ministry of Health and Prevention has granted approval for Leqembi (lecanemab), a humanized anti-soluble aggregated amyloid-beta (Aβ) monoclonal antibody, for the treatment of Alzheimer's disease (AD).
Leqembi is recommended for patients in the early stages of AD, specifically those with mild cognitive impairment (MCI) or mild dementia, as was the case in the clinical trials.
Leqembi targets and binds to both soluble Aβ aggregates (protofibrils) and insoluble Aβ aggregates (fibrils), which are key components of Aβ plaques. By doing so, it reduces the levels of both protofibrils and plaques in the brain.
This makes Leqembi the first approved treatment shown to slow the progression of the disease and to mitigate cognitive and functional decline through this specific mechanism.
In addition to its approval in the UAE, Leqembi is also approved in the U.S., Japan, China, South Korea, Hong Kong, and Israel and is marketed in these regions.
The approval in the UAE is based on data from the Phase 3 Clarity AD global study. In this study, Leqembi achieved its primary endpoint and all key secondary endpoints with statistically significant results. In the UAE, approximately 4.09% of individuals over the age of 60 are reported to have dementia, with Alzheimer's disease being the most common cause, accounting for 60-70% of cases.
Eisai is leading the global development and regulatory submissions for lecanemab, with both Eisai and Biogen sharing responsibilities for the commercialization and promotion of the product. In the UAE, Biogen will handle the commercialization of Leqembi.
Understanding Protofibrils and Their Role in Alzheimer’s Disease
Protofibrils are thought to be one of the most toxic forms of Aβ and are believed to play a critical role in the cognitive decline associated with Alzheimer’s disease. These protofibrils contribute to brain injury by damaging neurons, leading to a decline in cognitive functions. They not only promote the development of insoluble Aβ plaques but also directly damage brain cell membranes and the connections between nerve cells. Reducing protofibrils is believed to help prevent the progression of Alzheimer’s by minimizing neuronal damage and preserving cognitive function.
Lecanemab, a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody, was developed as part of a strategic research collaboration between Eisai and BioArctic. It is designed to target and neutralize both soluble protofibrils and insoluble forms of amyloid-beta (Aβ).
Key Findings from Leqembi’s Phase 3 Clarity AD Trial
The U.S. FDA granted approval to Leqembi based on data from Eisai’s global Phase 3 Clarity AD clinical trial.
The trial demonstrated that Leqembi significantly reduced clinical decline by 27% at 18 months compared to a placebo, as measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB). The baseline CDR-SB scores were similar between the two groups, with a mean score of approximately 3.2. After 18 months, the adjusted least-squares mean change from baseline was 1.21 in the Leqembi group and 1.66 in the placebo group, with a difference of −0.45.
Additionally, the secondary endpoint measured by the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) showed a 37% improvement in the Leqembi group compared to the placebo. The adjusted mean change from baseline in the ADCS-MCI-ADL score at 18 months was −3.5 in the Leqembi group and −5.5 in the placebo group. The ADCS-MCI-ADL scale evaluates a patient’s ability to perform daily activities independently, such as dressing, feeding themselves, and participating in community activities.
The most common adverse events reported in the Leqembi group were infusion reactions, ARIA-H (which includes cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headaches, and falls.
Leqembi’s Global Presence and Ongoing Research
Leqembi has been approved for treating mild cognitive impairment due to AD and mild AD dementia in the U.S., Japan, China, South Korea, Hong Kong, and Israel. Eisai has also submitted applications for approval in 11 additional countries and regions. A supplemental Biologics License Application (sBLA) for intravenous maintenance dosing was submitted to the U.S. FDA in March 2024, and the application was accepted in June 2024.
Additionally, a rolling submission for a Biologics License Application (BLA) for a subcutaneous injection formulation is underway, aiming to enhance patient convenience. This submission is being conducted under Fast Track status in the U.S. and began in May 2024.
Since July 2020, the Phase 3 AHEAD 3-45 study has been ongoing, focusing on individuals with preclinical AD who are clinically normal but have intermediate or elevated amyloid levels in their brains. The AHEAD 3-45 study is part of a public-private partnership between the Alzheimer’s Clinical Trial Consortium, the National Institute on Aging (NIA), and Eisai and Biogen. Furthermore, since January 2022, the Tau NexGen clinical study for Dominantly Inherited Alzheimer’s Disease (DIAD) has been ongoing, led by the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis, which includes lecanemab as the primary anti-amyloid therapy.
Eisai and Biogen’s Collaboration on Alzheimer’s Treatment
Eisai and Biogen have been working together on the development and commercialization of Alzheimer’s disease treatments since 2014. Eisai leads the global development and regulatory submissions for lecanemab, while both companies co-commercialize and co-promote the product, with Eisai having final decision-making authority.
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