Alzheimer's disease drug development in an evolving therapeutic landscape

The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA-approved amyloid plaque-lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape. The Alzheimer's Association Research Roundtable (AARR) Spring meeting held on May 23–34, 2023, brought together a broad array of scientific leaders from the AARR membership, academia, industry, and government and regulatory agencies to discuss the future of clinical trials in an era of regulator-approved amyloid-targeting therapies. Participants discussed lessons learned from other neurological diseases where disease-modifying treatments were first approved and key considerations for future clinical trials, for example, trial population real-world representativeness, duration, biomarker screening, efficacy endpoints, combination therapy, as well as overall trial design and the ethical and equity concerns that clinicians, patients, and their families face when considering clinical trial participation.

Highlights

• The Alzheimer's Association Research Roundtable (AARR) convened leaders from industry and academia, as well as patients, clinicians, and government and regulatory agency scientists to discuss the topic, “Alzheimer's Disease Drug Development in an Evolving Therapeutic Landscape.”
• While recently approved amyloid-targeting therapies show great promise in providing clinically meaningful outcomes for patients and families, additional treatments, and a better understanding of dosing and administration of these approved treatments, are needed to further slow and eventually prevent clinical decline in AD.
• Approved therapies will impact many aspects of clinical trial design including the use of placebo-controls, participant re-enrollment, safety monitoring, as well as biomarker selection.
• This exciting new era in AD research represents a hopeful future for clinicians, patients, and their care partners.