Three Key Take Reflections on the Recent Donanemab Approval

The last 20 years of drug development in Alzheimer’s disease reflect a coevolution of imaging agents and amyloid-targeting monoclonal therapies, informed by the amyloid hypothesis and predicated on the need for early intervention which, itself relies on early visualization of PET biomarkers.  This co-evolution is reflected in approval trends within the Alzheimer’s space: from accelerated approval based on the surrogate endpoint of amyloid plaque reduction (aducanumab), to surrogate endpoint-based accelerated approval followed by full approval using clinical endpoints (lecanemab) to, in the case of the July 2, 2024 donanemab decision, full approval based on clinical endpoints following an earlier rejection of accelerated approval.

What accounts for this recent pattern of approvals and what lessons can developers of Alzheimer’s disease therapies and imaging agents take from this history?

The trajectory reflects at least three key factors:   

1. Improvements in the technology of tau PET tracers could in principle lead to appreciable advances in the diagnosis and treatment of Alzheimer’s disease.  This is an area of active discovery with several sponsors of tau PET tracers currently poised to seek approval.  
2. Accelerated approval as a pathway to innovation is working, and arguably working particularly well in the case of AD where there is a mutually reenforcing need to develop better PET technologies to push the therapeutic window earlier and defend the cost of available therapy.
3. Three years and just about 3 months after the controversial approval of Aducanumab, it’s safe to say the field has advanced.  The door is not exactly wide open, but incremental progress is infinitely better than no progress. It begs the question of whether other challenging treatment modalities and indications might benefit from a similar approach.