Aducanumab produced a clinically meaningful benefit in association with amyloid lowering.

Aducanumab is a monoclonal antibody targeting amyl- oid beta protein (Aß), a defining feature of the biology of Alzheimer’s disease (AD) [1]. Laboratory studies showed high affinity of aducanumab for the neurotoxic oligomeric species of Aß [2]. Following a promising phase 1B trial [3], the sponsor (Biogen) implemented two phase 3 studies—EMERGE and ENGAGE. A planned futility analysis concluded that the treatment was not beneficial, and the trials were terminated. With the accrual of additional blinded data, the prespecified analysis of the primary outcome—Clinical Dementia Rating Sum of Boxes (CDR-sb)—showed that the EMERGE trial met its primary outcome and the EN- GAGE trial did not. Biogen submitted the data to the US Food and Drug Administration (FDA) for review and possible marketing approval, setting the stage for a vigorous dialogue on aducanumab.