Biogen and Eisai move forward with investigational Alzheimer's therapy
Following the approval of Aduhelm (aducanumab) by the FDA last year, lecanemab is the next most advanced candidate in Biogen and Eisai’s Alzheimer’s pipeline. Development of lecanemab is being led by Eisai, with Phase 3 trials currently in progress.
Like Aduhelm, lecanemab targets amyloid plaques in the brain: with the antibody binding to amyloid to reduce its presence and potentially slow the progress of the disease.
Phase 2 and 3 trials
Announced on December 23, the Fast Track designation for lecanemab follows Breakthrough Therapy designation granted by the FDA last year.
Breakthrough Therapy designation and Fast Track designation facilitate and expedite development of new drugs to address unmet medical need in the treatment of a serious or life-threatening conditions: such as Alzheimer's Disease
In September, Eisai initiated a rolling submission to the FDA of a Biologics License application (BLA) for lecanemab under the accelerated approval pathway. The BLA is based on clinical, biomarker and safety data from a Phase 2b clinical study in people with early Alzheimer’s Disease and confirmed amyloid pathology, and non-clinical and clinical parts of the application which consists of three parts (non-clinical, clinical and CMC) have already been submitted.
The approval of Aduhelm in the US - and subsequent rejection by the European Medicines Agency (EMA) - has been surrounded by questions over the efficacy of the drug. In rejecting the therapy’s application for authorisation last month, the EMA said that, ‘although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established.’
With lecanemab, the companies point to Phase 2b study results, which 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 that study ‘further supports Aβ as a surrogate endpoint that is reasonably likely to predict clinical benefit’.
(After 18 months, the Phase 2 study showed reduction of brain Aβ accumulation: as well as slowing disease progression as measured by ADCOMS, the study's measurement of clinical functions. However, the study failed to reach its 12 month primary outcome measure: which was set as an 80% or higher estimated probability of demonstrating 25% or greater slowing in clinical decline at 12 months treatment from baseline compared to placebo.)
The lecanemab Clarity AD Phase 3 clinical study in early Alzheimer’s completed enrollment in March 2021 with 1,795 patients: and the FDA has confirmed that the results of the study can be used to verify clinical benefit of lecanemab.
Another Phase 3 clinical study, AHEAD 3-45, is evaluating the efficacy of treatment with lecanemab in participants with preclinical Alzheimer’s Disease and elevated amyloid and in participants with early preclinical Alzheimer’s Disease and intermediate amyloid.
Eisai has also started a lecanemab subcutaneous dosing Phase 1 study.