Biomarkers as Endpoints in Clinical Trials for Alzheimer’s Disease

Article type: Research Article

Authors: Elghanam, Yomna^a | Purja, Sujata^a | Kim, Eun Young^{a; b; c; *}

Affiliations: [a] Department of Health, Evidence-Based and Clinical Research Laboratory, Social, and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, Seoul, Korea | [b] The Graduate School for Pharmaceutical Industry Management, College of Pharmacy, Chung-Ang University, Seoul, Korea | [c] The Department of Pharmaceutical Regulatory Sciences, Chung-Ang University, Seoul, Korea

Correspondence: [*] Correspondence to: Eun Young Kim, PhD, Professor, Head of department, Evidence-Based and Clinical Research Laboratory, Department of Health, Social and Clinical Pharmacy, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea; The Graduate School for Food and Drug Administration, The Graduate School for Regulatory Science, and The Graduate School for Pharmaceutical Industry Management, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea. Tel.: +82 2 820 5791; Fax: +82 2 816 7338; E-mail: [email protected].

Abstract: Background:Alzheimer’s disease (AD) is a neurodegenerative disease that imposes economic and societal burden. Biomarkers have played a crucial role in the recent approval of aducanumab and lecanemab as disease-modifying therapies which marked a significant milestone for the treatment of AD. The inclusion of biomarkers in AD trials facilitates precise diagnosis, monitors safety, demonstrates target engagement, and supports disease modification. Objective:This study analyzed the utilization state and trends of biomarkers as endpoints in AD trials. Methods:In this retrospective study, trials were collected by searching clinicaltrials.gov using the term “Alzheimer”. Primary and secondary outcomes were analyzed separately for each phase. Results:Among the 1,048 analyzed trials, 313 (29.87%) adopted biomarkers as primary endpoints and 364 (34.73%) as secondary endpoints, mainly in phases 1 and 2. The top three biomarkers adopted as primary endpoints in phases 1, 2, and 3 were amyloid-PET, tau-PET, and MRI. The top three biomarkers adopted as secondary endpoints, in phase 1, were cerebrospinal fluid (CSF) amyloid-β (Aβ), blood Aβ and amyloid-PET; in phase 2, they were MRI, CSF Aβ, and CSF phospho-tau; and in phase 3, they were amyloid PET, MRI, and blood Aβ. There was a statistically significant increase in the adoption of biomarkers as primary endpoints in phase 2 trials (p = 0.001) and secondary endpoints in phase 3 trials (p = 0.001). Conclusions:The growing recognition of the importance of biomarkers in AD trial’ design and drug development is evident by the significant steady increase in biomarkers’ utilization in phases 2 and 3.

Keywords: Alzheimer’s disease, amyloid, biomarkers, clinical trials, drug development, endpoint, tau

DOI: 10.3233/JAD-240008

Journal: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 693-703, 2024