Trends in clinical studies evaluating neurofilament light chain as a biomarker

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.

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.

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.

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.