Eisai and Biogen Initiate Rolling BLA Submission to FDA for Lecanemab in Early Alzheimer's Disease

On September 27, Eisai announced that it has initiated a rolling submission of the Biologics License Application (BLA) for its investigational Alzheimer’s disease (AD) antibody therapy, lecanemab, to the U.S. FDA via the accelerated approval pathway for the treatment of early AD. In June this year, lecanemab was granted Breakthrough Therapy designation by the U.S. FDA. Subsequently, Eisai reached an agreement with the U.S. FDA to submit the BLA for lecanemab on a rolling basis under the accelerated approval pathway. A PDUFA date will be set once all sections of the application have been submitted and accepted by the FDA.

The marketing application is primarily based on the clinical, biomarker, and safety data from the Phase 2b clinical trial (Study 201) of lecanemab in patients with early Alzheimer's disease (AD). The trial enrolled 856 patients with mild cognitive impairment (MCI) due to AD or mild AD, with confirmed amyloid pathology. The results demonstrated that lecanemab at the highest dose (10 mg/kg) significantly reduced brain amyloid levels, achieving a reduction of 0.306 standardized uptake value ratio (SUVr) units at 18 months of treatment (baseline mean: 1.37). Additionally, patients who initially received placebo also showed decreased amyloid levels after switching to lecanemab during the trial's extension phase. Furthermore, lecanemab was well tolerated, with a 9.9% incidence of amyloid-related imaging abnormalities (ARIA), edema, and effusion at a dose of 10 mg/kg administered every two weeks.

The Phase 3 clinical trial of lecanemab for early AD (Clarity AD) is ongoing, with the enrollment of 1,795 patients completed in March 2021. The U.S. FDA has agreed that the final results of this clinical trial can serve as a confirmatory study to verify the clinical benefit of lecanemab, further supporting the BLA.

Lecanemab (BAN2401) is a humanized monoclonal antibody intended for the treatment of AD, developed through a collaboration between Eisai and BioArctic AB. Lecanemab selectively binds to, neutralizes, and eliminates soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils), which are believed to accelerate the neurodegenerative process in AD. Therefore, lecanemab may modify disease pathology and slow disease progression.

Under the agreement signed between Eisai and BioArctic in December 2007, Eisai obtained global rights to research, develop, manufacture, and commercialize lecanemab for the treatment of AD;

In March 2014, Eisai and Biogen signed a joint development and commercialization agreement for lecanemab, which was amended by both parties in October 2017. Currently, based on the results of the Phase II clinical trial (Study 201), the pivotal Phase III clinical trial of lecanemab for symptomatic early AD (Clarity-AD) is underway;

In July 2020, a Phase 3 clinical trial (AHEAD 3-45) was initiated for individuals with preclinical AD (who are clinically normal but have moderate or elevated amyloid levels in the brain). The AHEAD 3-45 study is being conducted through a public-private partnership between the Alzheimer’s Clinical Trials Consortium, funded by the National Institute on Aging (a division of the U.S. National Institutes of Health), and Eisai.

(Original text abridged)

References:

[1] Eisai Initiates Rolling Submission To The U.S. FDA For Biologics License Application Of Lecanemab (BAN2401) For Early Alzheimer's Disease Under The Accelerated Approval Pathway. Retrieved 2021-09-28, from https://www.prnewswire.com/news-releases/eisai-initiates-rolling-submission-to-the-us-fda-for-biologics-license-application-of-lecanemab-ban2401-for-early-alzheimers-disease-under-the-accelerated-approval-pathway-301386121.html