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FDA Advisory Committee does not recommend approval of Aducanumab

Friday 06 November 2020

Aducanumab, a monoclonal β-amyloid antibody, has been evaluated in several clinical trials on mild Alzheimer’s disease and mild cognitive impairment, including the ENGAGE, EMERGE and PRIME trials.  Since 7 August, Aducanumab has been under priority review at the US Food and Drug Administration (FDA).

On 6 November, the FDA discussed Aducanumab during a meeting of the Peripheral and Central Nervous Systems Drugs Advisory Committee, which is charged with reviewing and evaluating data concerning the safety and efficacy of drugs for Alzheimer’s disease (AD) and other neurological indications. The FDA Advisory Committees provide non-binding recommendations to the FDA, which usually follows these recommendations when considering whether to approve drugs.  The 6 November meeting was held virtually and broadcast live online, with the FDA encouraging public attendance via the webcast as well as public submissions to the Committee prior to the event.

During the 7 hour-long meeting, representatives from Biogen and the FDA Division of Neurology delivered presentations on the efficacy and safety of Aducanumab based on data from EMERGE, ENGAGE and PRIME. The results of an FDA statistical review of these data were also presented, followed by an open public hearing during which submissions from advocacy groups, patient associations and other third parties were heard.  The broadly positive findings of the FDA Division of Neurology contrasted with the negative report from the FDA biostatistical review, which identified flaws and inconsistencies in the results. 

11 members of the 17-strong Advisory Committee (which includes patient and consumer representatives alongside experts on biostatistics, neurology and epidemiology) had voting rights during the meeting, and were called upon to vote on four questions.  The first question asked whether the positive EMERGE study - independent of the negative ENGAGE study - provided strong evidence to support the effectiveness of Aducanumab for the treatment of AD.  To this question, the committee voted 1-yes, 8-no and 2-uncertain. 

The second question asked whether the Phase 1b PRIME study provided supportive evidence on the effectiveness of Aducanumab for the treatment of AD. To this question, the committee voted 0-yes, 7-no and 4-uncertain.

The third question asked whether there was strong evidence of a pharmacodynamic effect of aducanumab on AD pathophysiology (e.g β-amyloid or Tau accumulation in the brain).  This question garnered the most positive responses from the Committee, which voted 5-yes, 0-no and 6-uncertain.

 Finally, the fourth question asked whether, given the results of ENGAGE, EMERGE and PRIME, and the evidence of a pharmacodynamic effect of Aducanumab on AD pathophysiology, it was reasonable to consider EMERGE alone as primary evidence of effectiveness.  To this question, 10 Committee members voted no, with one uncertain vote.

The FDA will now continue the review process, with a final decision on approval due by 7 March 2021.

Presentations, transcripts and other materials for the FDA Advisory Committee meeting can be found here:

https://www.fda.gov/advisory-committees/advisory-committee-calendar/november-6-2020-meeting-peripheral-and-central-nervous-system-drugs-advisory-committee-meeting

https://investors.biogen.com/news-releases/news-release-details/update-fda-advisory-committees-meeting-aducanumab-alzheimers

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