Ligand id: 8325

Name: aducanumab

No information available.
Summary of Clinical Use
Preliminary results from Phase 1 trial NCT01677572, published in Nature in September 2016 [5], suggested the antibody reduces brain Aβ in a dose- and time-dependent manner, and this led to continued progression, culminating in Phase 3 clinical trials to evaluate aducanumab's effect on cognitive decline in AD patients (see EMERGE NCT02484547 and ENGAGE NCT02477800). Futility analysis (i.e. concluding that the antibody would not delay cognitive decline) led to the decision by aducanumab's developer Biogen, to terminate these trials but to complete patient follow-ups and closing out activities. Although designed as a duplicate of EMERGE, ENGAGE failed to replicate the efficacy seen in EMERGE. Following anaysis of the larger dataset collected from all of the patients from both trials who completed 18 months follow up, Biogen claimed that extended exposure to the higher 10 mg/kg dose used in their trials is effective, and they declared their intention to seek FDA approval for this treatment regimen in early 2020 [1]. Biogen's claims about aducanumab's efficacy are being scrutinised, particularly in light of the conflicting results from EMERGE and ENGAGE and because quantitative raw data is not (yet) available for independent examination [3-4].
Mechanism Of Action and Pharmacodynamic Effects
Epitope mapping reveals that aducanumab (BIIB037) binds to residues 3-6 of human Aβ [2]. In vivo studies show that chronic administration of the antibody in mice induces microglia-mediated clearance of amyloid plaques [2].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01677572 Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease Phase 1 Interventional Biogen
NCT02477800 221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease Phase 3 Interventional Biogen
NCT02484547 221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease Phase 3 Interventional Biogen