Perspective Accelerating Alzheimer's therapeutic development: The past and future of clinical trials

Alzheimer's disease (AD) research has entered a new era with the recent positive phase 3 clinical trials of the anti-Ab antibodies lecanemab and donanemab. Why did it take 30 years to achieve these successes? Devel-oping potent therapies for reducing fibrillar amyloid was key, as was selection of patients at relatively early stages of disease. Biomarkers of the target pathologies, including amyloid and tau PET, and insights from past trials were also critical to the recent successes. Moving forward, the challenge will be to develop more efficacious therapies with greater efficiency. Novel trial designs, including combination therapies and umbrella and basket protocols, will accelerate clinical development. Better diversity and inclusivity of trial participants are needed, and blood-based biomarkers may help to improve access for medically under-served groups. Incentivizing innovation in both academia and industry through public-private partnerships, collaborative mechanisms, and the creation of new career paths will be critical to build momentum in these exciting times.

Automated summary

Recent positive phase 3 clinical trials of anti-Ab antibodies have brought new advancements in Alzheimer's disease research. The key factors for success include developing potent therapies, selecting patients at early stages, biomarkers, and insights from past trials. The challenge ahead is to develop more efficacious therapies and improve diversity and inclusivity of trial participants.