PI-003 - BIOMARKER UTILIZATION IN NEUROLOGICAL DRUG PRODUCTS APPROVED BY FDA (2008-2023): A LANDSCAPE ANALYSIS.

D. Jung¹, S. Sabarinath², R. Uppoor², M. Mehta², Y. Zhang²; ¹University of Illinois Chicago, Chicago, IL, USA, ²U.S. Food and Drug Administration, Silver Spring, MD, USA.

Background: Neurological diseases have devastating effects on patients and caregivers, posing a significant global health burden. However, these diseases are often characterized by complex disease pathophysiology with heterogeneous disease traits and progression, creating significant challenges for drug development. Biomarkers, as an indicator of pathogenic processes or responses to therapeutic interventions, have the potential to serve as the basis for drug development and regulatory decision making, particularly in the field of neurology. There has been increasing interest in using biomarkers to support drug development and regulatory decision-making in recent years.

Methods: A list of neurology NME products approved from 2008 to 2023 was obtained from the FDA’s database “CDER Novel Drug Approvals Dashboard”. Biomarker-related information was manually extracted from the documents available on Drugs@FDA website, focusing on clinical pharmacology review, clinical review, multidisciplinary integrated review, and labeling. The utility of biomarkers for each product were summarized.

Results: Among the 65 neurological NMEs approved between 2008 and 2023, around half of them had biomarker data described in the FDA regulatory reviews. Over the years, the utilization of biomarkers in drug applications has increased significantly. Biomarkers have been playing various roles in drug development and regulatory decision-making, such as (1) serving as surrogate endpoint for accelerated approval; (2) providing confirmatory evidence for demonstrating effectiveness; (3) supporting clinical trial design and dose selection. The proportion of NME approvals utilizing biomarker data varies by indication and drug modality. The challenges for effective use of the biomarker data arose from multiple aspects, such as clinical relevance, bioanalytical validation, and data quality.

Conclusion: Biomarkers have been increasingly used in the development and regulatory approval of NMEs for the treatment of neurological diseases, with multiple roles such as surrogate endpoints, confirmatory evidence, and basis for dose selection. This landscape analysis provides valuable insights on current progress in the use of biomarkers, towards the goal of unleashing the power of biomarker data.