Eisai Co and Biogen Inc announced that Eisai has initiated a rolling submission to the U.S. Food and Drug Administration (FDA) of a Biologics License Application (BLA) for lecanemab (BAN2401), the company’s investigational anti-amyloid beta (Aβ) protofibril antibody, for the treatment of early Alzheimer’s disease (early AD).

The BLA is being submitted under the accelerated approval pathway and is primarily based on clinical, biomarker and safety data from the Phase 2b clinical trial in people with early AD and confirmed amyloid pathology. The lecanemab Phase 2b trial results demonstrated a high degree of Aβ plaque lowering and consistent reduction of clinical decline across several clinical endpoints. The correlation between the extent of Aβ plaque reduction and effect on clinical endpoints in Study 201 further supports Aβ as a surrogate endpoint that is reasonably likely to predict clinical benefit. AD is a serious, progressive and devastating disease with few treatment options. Eisai is utilizing the accelerated approval pathway after discussion with the FDA and aims to bring a new treatment option to people living with early AD, their families and healthcare professionals. 

In June 2021, lecanemab was granted Breakthrough Therapy designation, which is an FDA program intended to expedite the development and review of medicines for serious or life-threatening conditions. Eisai has an agreement with the FDA to submit the BLA for lecanemab as a rolling submission. This agreement allows completed portions of the application to be submitted to the FDA for review on an ongoing basis. After all portions are submitted to the FDA and the agency accepts the BLA, the Prescription Drug User Fee Act (PDUFA) action date (target date for completion of examination) will be set. 

The BLA submission for lecanemab is primarily based on the results of the proof-of-concept Study 201 in 856 patients with mild cognitive impairment (MCI) due to AD and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology. The results were published in a peer-reviewed journal in April 2021. Study 201 explored the impact of treatment with lecanemab on reducing brain Aβ and clinical decline. At 18 months of treatment, 10 mg/kg biweekly lecanemab reduced brain amyloid by 0.306 SUVr units (from a baseline mean of 1.37), and over 80% of subjects became amyloid negative by visual read. Furthermore, the extent of reduction in amyloid was correlated with slower clinical decline on ADCOMS (Alzheimer’s Disease Composite Score), CDR-SB (Clinical Dementia Rating-Sum-of-Boxes), and ADAS-cog (Alzheimer Disease Assessment Scale-Cognitive Subscale) at the treatment group and patient level. The rate of amyloid-related imaging abnormalities-oedema/effusion (ARIA-E), an adverse event associated with amyloid targeted therapies, for the 10 mg/kg biweekly dosing was 9.9%.

For many years, Eisai has endeavoured to understand the anxieties of people living with AD and has been conducting research and development of novel therapies,” said Haruo Naito, Chief Executive Officer at Eisai Co., Ltd. “The lecanemab rolling BLA submission marks a new milestone toward the advancement of a treatment system for AD. As part of our human health care mission, we are committed to bringing new medicines to people living with AD and their families as early as possible.”

“It is our vision that patients and their families have choice and access to multiple treatment options for Alzheimer’s disease. The rolling submission of lecanemab for FDA review under the accelerated pathway is a positive step toward that goal,” said Michel Vounatsos, Chief Executive Officer at Biogen.