Biogen and it’s collaborative partner Eisai announced they are discontinuing the global Phase 3 trials, ENGAGE and EMERGE, designed to evaluate the efficacy and safety of aducanumab in patients with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease dementia.
ENGAGE and EMERGE are global multicenter, randomized, double-blind, placebo-controlled, parallel-group studies. The primary objective was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. The decision to stop the trials was based on results of a futility analysis conducted by an independent data monitoring committee. The analysis indicated the trials were unlikely to meet their primary endpoint upon completion. The recommendation to stop the studies was not based on safety concerns. Detailed data from the ENGAGE and EMERGE studies will be presented at future medical meetings. As part of this decision, the EVOLVE Phase 2 safety study and the long-term extension of the PRIME Phase1b study of aducanumab will also be discontinued.
About Alzheimer’s disease
Alzheimer’s disease is a progressive disorder that causes brain cells to degenerate and die. It is believed to be caused by a combination of genetic, lifestyle and environmental factors that affect the brain over time. Two proteins are implicated in the progression of Alzheimer’s disease, Beta-amyloid and tau proteins. Beta-amyloid is a leftover fragment of a larger protein. When these fragments cluster together, they appear to have a toxic effect on neurons and to disrupt cell-to-cell communication. These clusters form larger deposits called amyloid plaques, which also include other cellular debris. Tau proteins play a part in a neuron’s internal support and transport system to carry nutrients and other essential materials. In Alzheimer’s disease, tau proteins change shape and organize themselves into structures called neurofibrillary tangles. The tangles disrupt the transport system and are toxic to cells.
Aducanumab is a human monoclonal antibody (mAb), developed using Neurimmune’s technology platform called Reverse Translational Medicine (RTM). It preferentially binds to the aggregated amyloid beta (Aβ) as it targets an epitope (a small section of the protein that the antibody recognizes) that is not normally accessible in the Aβ monomer. Through this interaction, aducanumab reduces the number of amyloid plaques present in the brain. The treatment was originally developed by Neurimmune which, after entering a partnership with Biogen in 2007, granted Biogen the license for future development and commercialization of aducanumab. Biogen entered into a collaboration with Eisai in October 2017.