Eisai Completes Rolling BLA Submission to FDA for Lecanemab as Potential Successor to Aduhelm in Early Alzheimer’s Disease

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Recently, Eisai and Biogen jointly announced that Eisai has submitted a Biologics License Application (BLA) for lecanemab (BAN2401) to the U.S. FDA under the accelerated approval pathway for biologics. Lecanemab is an investigational anti-amyloid beta (Aβ) protofibril antibody intended for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD (collectively referred to as early AD) in patients confirmed to have amyloid pathology in the brain. In June and December 2021, the FDA granted lecanemab Breakthrough Therapy designation and Fast Track designation, respectively.

It is worth mentioning that previously, Biogen's first Alzheimer's drug Aduhelm faced repeated setbacks, continuous controversy, and its performance after launch was below expectations. As a result, Eisai withdrew from the market expansion related to Aduhelm and focused on the development of lecanemab. Biogen has stated that in the future, it will continue to collaborate with Eisai to develop a second Alzheimer's disease drug, lecanemab. (For details, please click: After Biogen's Aduhelm encountered obstacles: CEO to step down, betting on the second Alzheimer's therapy lecanemab)

Currently, Eisai is submitting lecanemab through the accelerated approval pathway. The phase 3 confirmatory Clarity AD clinical trial, which involves 1,795 patients, is expected to report results this fall. The FDA has agreed that, upon completion of the Clarity AD trial, its results can serve as the confirmatory study to validate the clinical efficacy of lecanemab. Based on the results of the Clarity AD clinical trial, Eisai will submit a full approval application for lecanemab to the FDA in the fiscal year 2022.

Lecanemab is a humanized monoclonal antibody used to treat AD, which selectively binds, neutralizes, and eliminates soluble, toxic Aβ aggregates (protofibrils). These aggregates are believed to accelerate the neurodegenerative process of AD. Therefore, lecanemab may have an impact on disease pathology and slow down the progression of the disease. Currently, lecanemab is being developed as the only anti-Aβ antibody that can be used to treat early AD without titration.

Eisai leads the development and regulatory submissions for lecanemab globally, while Eisai and Biogen jointly commercialize and co-promote the product, with Eisai having the final decision-making authority.

The BLA submission for lecanemab is based on clinical, biomarker, and safety data from 856 early AD patients with confirmed amyloid pathology in the proof-of-concept Phase 2b Study 201 Core, as well as biomarker and safety data from the Study 201 OLE (Open-Label Extension study, 180 patients), and blinded safety data from the confirmatory Clarity AD Phase 3 study (1795 patients).

The large number of patients in these studies provided the FDA with extensive safety data. Study 201 explored the impact of lecanemab treatment on reducing amyloid plaques and clinical decline. The data showed that lecanemab (10 mg/kg, once every two weeks) significantly reduced amyloid protein levels in the brain. After 18 months of treatment, the average reduction in brain amyloid was 0.306 SUVr units (baseline average was 1.37), and over 80% of patients were amyloid-negative as measured by PET.

In addition, the degree of amyloid reduction was associated with a slower rate of clinical decline as measured by the Alzheimer's Disease Composite Score (ADCOMS), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) at both the treatment group and patient levels. In the Core study, the overall incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid beta antibody treatment, was 9.9% (16/161) in the lecanemab (10 mg/kg biweekly) treatment group compared to 0.8% (2/245) in the placebo group.

Reference Source: EISAI COMPLETES ROLLING SUBMISSION TO THE U.S. FDA FOR BIOLOGICS LICENSE APPLICATION OF LECANEMAB FOR EARLY ALZHEIMER'S DISEASE UNDER THE ACCELERATED APPROVAL PATHWAY