As the industry paints an increasingly clearer picture for Alzheimer’s disease pathologies, treatments are becoming more inclusive of non-pharmacological lifestyle changes, while clinical trials are moving towards optimised operations.
Experts deliberated these and other Alzheimer’s disease drug development trends at the 2024 Alzheimer's Association International Conference (AAIC), being held 28 July – 1 August in Philadelphia, Pennsylvania.
Mechanistically, the field has a better understanding of the distinct Alzheimer’s pathologies—specifically related to amyloid and tau—and has developed multiple effective approaches to address these pathologies, said Dr. Eric McDade, professor of Neurology at Washington University School of Medicine in St. Louis, Missouri, at a discussion on 29 July. This offers the opportunity to not only move forward with combination therapies that target different pathologies but also develop combinations that could sequentially target the same pathology, he says. This could improve adverse effects and help with chronic use, he added.
The availability of biological disease modifying drugs such as Eisai and Biogen’s Leqembi (lecanemab) and Eli Lilly’s Kisunla (donanemab) is fundamentally changing the way the field characterises Alzheimer’s, said McDade. Furthermore, not integrating these therapies into future clinical trials would be a “major issue or deficiency.”
While Eli Lilly made strides earlier this month with an FDA approval for its amyloid-targeting therapy, Eisai and Biogen announced today (29 July) that the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion on the Marketing Authorization Approval (MAA) for Leqembi in the EU.
Alongside pharmacological treatments, increasing attention is being brought to implementing non-pharmacological lifestyle changes as a means to address the chronic condition. So far, the field has learned that patients gain a small cognitive benefit from addressing exercise, diet, social engagement separately, said Laura Baker, PhD, professor of Gerontology and Geriatric Medicine at the Wake Forest University School of Medicine, Salem, North Carolina. However, the field is moving towards a multi-domain, multi-component approach that allows for the evaluation of synergistic effects that cannot be evaluated in single-domain testing, she added.
Also challenging for Alzheimer’s clinical trials field is navigating increasing trial costs, combating trial failure rates, and balancing speed and quality of information, said Suzanne Hendricks, CEO of the Millcreek, Utah-based consultancy Pentara Corporation.
“Clinical trials are expensive and slow. And I think this is a case where Alzheimer's disease is probably more expensive and even slower,” Hendricks explained. She went on to share how implementing basket trials could reduce redundancy and improve efficiency while utilising platform trials could reduce trial costs and optimise trials for speed.
