Trends in clinical studies evaluating neurofilament light chain as a biomarker

Abstract

Introduction: The use of biomarkers as surrogate endpoints, supported by strong mechanistic, epidemiologic, and/or clinical data, provides drug development programs with endpoints that predict clinical benefit and may be more sensitive to drug effects than clinical endpoints. Neurofilament light chain (NfL) is a marker of neuroaxonal injury that has emerged as a promising biomarker for neurodegenerative diseases. Methods: We identified Investigational New Drug programs submitted to the U.S. Food and Drug Administration between 2005–2024 that proposed to use NfL as a pharmacodynamic biomarker, biomarker for patient selection or stratification, and/or surrogate endpoint for accelerated approval. Results: A total of 50 programs were identified with most from the last five years. Of the 50 programs, 94% (n = 47) proposed NfL as a pharmacodynamic biomarker, 8% (n = 4) for patient selection, 52% (n = 26) for patient stratification, and 20% (n = 10) as a surrogate endpoint. Of the programs evaluating NfL as a pharmacodynamic biomarker with available data on NfL levels (n = 21), approximately 50% reported NfL changes that correlated with drug exposure. Conclusion: This analysis highlights the important role that NfL plays in clinical trials and identifies future areas of research and study design considerations to strengthen the support of NfL as a biomarker.