Aducanumab, the most promising new dementia drug of the past two decades, has failed to obtain the widely expected FDA approval in early November, with a decision now delayed until next year.

This follows the FDA scientific advisory committee’s recommendation not to approve the drug on the basis that, in their view, the data presented did not provide strong evidence to support the efficacy of aducanumab for treating Alzheimer’s disease when viewed independently.

While the committee’s recommendation is not binding, the FDA usually follows it.

The FDA is now evaluating aducanumab under Priority Review, with a decision on whether to approve the drug by 7 March 2021.

If the FDA approves aducanumab, it will become the first medicine to be approved to reduce the clinical decline associated with Alzheimer’s disease. It will also be the first medicine to show that removing amyloid beta (plaque in the brain) results in better clinical outcomes in Alzheimer’s patients.

Background:

• Aducanumab is a monoclonal antibody thought to work by facilitating the clearance of insoluble amyloid plaques from the brain. It is given by monthly IV infusion.
• In March 2019 Biogen announced discontinuation of their Phase III EMERGE and ENGAGE studies in patients with early AD following a futility analysis
• In October 2019 announced they planned to proceed with FDA approval based on analysis of a larger dataset that became available only after the studies were stopped, that showed EMERGE (not ENGAGE) in fact did meet its primary endpoint of reduction in clinical decline for patients on the highest dose of the drug
• They also said that while ENGAGE did not meet its primary endpoint, there were trends for patients receiving the highest dose that were consistent with what was seen in EMERGE.