A setback in Alzheimer's Medicine: Biogen and Eisai Discontinue Phase 3 Trials of Aducanumab in Alzheimer's Disease
Who doesn't love monoclonal antibodies (mAbs)? The vanguard of cellular specificity, these protein machines speed around with monovalent affinity and bind selectively. The latest developments in Alzheimer's research have led to a mAb that can selectively attack structures related to the disease, but the companies researching the clinical uses of the biologic compound are no longer certain that trials will yield meaningful results.
To quote the company:
Biogen and Eisai, Co., Ltd. today announced the decision to discontinue 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. The decision to stop the trials is based on results of a futility analysis conducted by an independent data monitoring committee, which indicated the trials were unlikely to meet their primary endpoint upon completion. The recommendation to stop the studies was not based on safety concerns.
To clarify, "endpoints" are quantifiable results that are measured during trials to implement a statistical qualification for success.
Where did Biogen get its hands on this monoclonal antibody treatment? Who owns the patent?
Biogen licensed aducanumab from Neurimmune under a joint development and license agreement.
How was this biologic compound discovered?
Aducanumab is a human monoclonal antibody (mAb) derived from ... cells collected from healthy elderly subjects with no signs of cognitive impairment or cognitively impaired elderly subjects with unusually slow cognitive decline using Neurimmune’s technology platform called Reverse Translational Medicine (RTM).
How does the RTM platform work?
Researchers find healthy subjects and gauge their response to disease-related proteins, looking for common antibody presence. Then they take them. Think vampires.
Is Neurimmune's RTM platform for isolating immunotherapeutics a reliable way of finding effective, specific, and appropriate immunotherapeutics?
Is a mechanism of action presented along with candidate antibodies through RTM?
Is there any real advantage in discovering antibodies through RTM?
At the very least, what we know cannot hurt us. They're guaranteed 100% human.
Nature published an article related to this antibody back in 2016 (see The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease, Nature). The research demonstrated that "In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner," but the recent futility analysis conducted by an independent data monitoring committee discouraged the manufacturer from pursuing extensive clinical trials. The use of immunostaining of "autopsy tissue from patients with AD ... confirmed binding of aducanumab to bona fide human Aβ fibrils" and brought one of many promising findings delivered in the paper.
Clearly, there is much left to understand about neuroscience and the Amyloid β amino acid chains of roughly 40 residues that constitute the amyloid plaques found in the brains of Alzheimer patients. Even global Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies are not too big to fail. Even when they made it onto a Nature Cover.