FDA Grants Fast Track Designation to Lecanemab, an Investigational Anti-Amyloid Beta Protofibril Antibody for Alzheimer’s Disease

December 24, 2021 /BioValleyBIOON/ -- Eisai and its partner Biogen recently announced jointly that the U.S. Food and Drug Administration (FDA) has grantedlecanemab（BAN2401）Fast Track Designation (FTD), which is a research-basedAnti-β-Amyloid (Aβ) Fibril Antibody, for the treatment of Alzheimer's disease (AD). In June this year,FDAAlso granted lecanemab Breakthrough Therapy Designation (BTD).

BTD and FTD are two new drug review channels of the FDA, aimed at promoting and accelerating new drug development to address unmet medical needs in the treatment of serious or life-threatening diseases (such as AD), and providing withFDAOpportunities for frequent interaction.

In September 2021, Eisai submitted under the accelerated approval pathway toFDAA Biologics License Application (BLA) has been submitted. The BLA is primarily based on clinical, biomarker, and safety data from a Phase 2b clinical study (Study 201) conducted in patients with early AD, confirming amyloid pathology. The non-clinical and clinical sections of the application (three sections: non-clinical, clinical, CMC) have been submitted. Results from the Phase 2b study indicate,Lecanemab treatment significantly reduced brain β-amyloid (Aβ) plaques and continuously decreased multiple clinical andBiomarkerClinical decline at the endpoint. In Study 201, the correlation between the degree of Aβ plaque reduction and its impact on clinical endpoints further supports Aβ as a surrogate endpoint, reasonably predicting clinical benefit.

The Phase 3 clinical study of lecanemab Clarity AD in early AD patients is ongoing, with the enrollment of 1,795 patients completed in March 2021.FDAAgree that the results of Clarity AD can serve as a confirmatory study to validate the clinical efficacy of lecanemab after completion. The blinded safety data from the Clarity AD study have been included to support the ongoing rolling submission. Another Phase 3 clinical study (AHEAD 3-45) is evaluating the efficacy of lecanemab in patients with preclinical Alzheimer's disease (AD) who have elevated brain amyloid levels, as well as in patients with early preclinical AD and moderate amyloid levels. Additionally, Eisai has initiated a Phase 1 study on subcutaneous administration of lecanemab.

It is worth mentioning that, in June 2021, Eisai and Biogen collaborated to develop aAnti-β-Amyloid Antibody Aduhelm (Aducanumab)Obtained in the United StatesFDAApproved for the treatment of AD.Aduhelm represents the first drug in its class to be approved for the treatment of AD, marking the first new therapy for AD since 2003 and the first treatment targeting the underlying pathophysiology of AD, signifying a major milestone in the treatment of AD.

AD is an irreversible, progressive brain disease that slowly destroys a person's memory and thinking skills, and eventually the ability to carry out simple tasks. While the exact cause of AD is not fully understood, it is characterized by changes in the brain, including amyloid plaques and neurofibrillary (tau) tangles, leading to the loss of neurons and their connections. These changes affect a person's memory and thinking abilities.

Aduhelm is the first treatment to target and affect the underlying course of AD.Researchers evaluated the efficacy of Aduhelm in three separate studies involving a total of 3,482 patients. These studies included double-blind, randomized, placebo-controlled dose-ranging trials in AD patients. Patients receiving Aduhelm showed a significant dose- and time-dependent reduction in amyloid beta plaques, while patients in the control group did not show a reduction in amyloid beta plaques.

These results support the accelerated approval of Aduhelm,This approval is based on the surrogate endpoint of reduced amyloid-beta plaques in the brain, a hallmark characteristic of AD.In the study, positron emission tomography (PET) imaging was used to quantify amyloid β plaques in order to estimate the levels of amyloid β plaques in brain regions expected to be widely affected by AD pathology, and to compare them with brain regions not expected to be affected by such pathology.

The prescribing information for Aduhelm includes a warning about amyloid-related imaging abnormalities (ARIA), which typically manifest as temporary swelling in areas of the brain, usually resolving over time without causing symptoms, although some patients may experience symptoms such as headache, confusion, dizziness, vision changes, or nausea. Another warning for Aduhelm is the risk of allergic reactions, including angioedema and urticaria. The most common side effects of Aduhelm are ARIA, headache, falls, diarrhea, and confusion/delirium/altered mental status/disorientation. (Bioon.com)

Source of the original text:INVESTIGATIONAL ALZHEIMER'S DISEASE THERAPY LECANEMAB GRANTED FDA FAST TRACK DESIGNATION