Why were Aduhelm's clinical trial results considered unreliable?
Both phase 3 trials were stopped as futile in March 2019; Biogen later reanalysed a larger dataset and found benefit in only one trial. The FDA's own statistical team said the evidence was insufficient — so the agency approved on the surrogate endpoint instead.
Biogen ran two large phase 3 trials, EMERGE and ENGAGE. In March 2019, Biogen cancelled both trials after an independent analysis concluded the drug was unlikely to slow cognitive and functional decline and that further study would be futile. Later that year Biogen reanalysed a larger dataset and argued that the high dose showed benefit in EMERGE, although ENGAGE remained negative. Having one positive and one negative trial, with the positive result emerging only after a futility stop, is a weak evidentiary basis. The FDA's own statistical team argued there was insufficient evidence of Aduhelm's benefits. The agency's decision to approve on amyloid reduction, rather than on the disputed clinical endpoints, effectively sidestepped this problem, which critics argued undermined the purpose of requiring confirmatory evidence.