FDA's accelerated approval pathway under continued post-Aduhelm scrutiny

Aducanumab's accelerated approval in 2021, the controversies that followed, and the sponsor's voluntary withdrawal of the product in 2024 have not been forgotten inside the FDA. Subsequent advisory committees on Alzheimer's therapies have engaged surrogate-endpoint questions more sharply than they did before - particularly the relationship between amyloid clearance and clinical benefit.

For sponsors, the practical implications are concrete:

• Confirmatory trial design matters earlier. Accelerated-approval submissions are increasingly accompanied by post-marketing trial designs that the agency has already engaged with.
• Biomarker-only approvals are no longer the default expectation for the next wave of mechanisms.
• Public statements from advisors carry more weight, influencing pricing negotiations and payor coverage decisions even before final action.

This is not a closed door - donanemab's 2024 traditional approval used clinical endpoints and was non-controversial. It is a recalibrated bar, and one that anyone modelling future Alzheimer's pipeline economics should price in. The related argument over whether small CDR-SB deltas are clinically meaningful - covered in our Signal on the CDR-SB meaningfulness debate - sits inside the same regulatory conversation, and the shift toward registry data as the binding signal is changing what "confirmatory evidence" is going to mean in practice.