학술논문
Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.
Document Type
Academic Journal
Author
Benatar M; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.; Ostrow LW; Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.; CReATe Biomarkers External Advisory Committee.; Lewcock JW; CReATe Biomarkers External Advisory Committee.; Denali Therapeutics, South San Francisco, CA, USA.; Bennett F; CReATe Biomarkers External Advisory Committee.; Ionis Pharmaceuticals, Carlsbad, CA, USA.; Shefner J; CReATe Biomarkers External Advisory Committee.; Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.; Bowser R; CReATe Biomarkers External Advisory Committee.; Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, USA.; Larkin P; The ALS Association, Arlington, VA, USA.; Bruijn L; CReATe Biomarkers External Advisory Committee.; Novartis Pharmaceuticals UK, London, UK.; Wuu J; Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA.
Source
Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7707449 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-8249 (Electronic) Linking ISSN: 03645134 NLM ISO Abbreviation: Ann Neurol Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: To explore whether the utility of neurofilament light chain (NfL), as a biomarker to aid amyotrophic lateral sclerosis (ALS) therapy development, would be enhanced by obtaining formal qualification from the US Food and Drug Administration for a defined context-of-use.
Methods: Consensus discussion among academic, industry, and patient advocacy group representatives.
Results: A wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts-of-use, the US Food and Drug Administration has provided accelerated approval for an SOD1-lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.
Interpretation: The increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility-as a prognostic, response, risk/susceptibility, and/or safety biomarker-is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer-reviewed data-absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts-of-use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211-216.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Methods: Consensus discussion among academic, industry, and patient advocacy group representatives.
Results: A wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts-of-use, the US Food and Drug Administration has provided accelerated approval for an SOD1-lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.
Interpretation: The increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility-as a prognostic, response, risk/susceptibility, and/or safety biomarker-is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer-reviewed data-absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts-of-use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211-216.
(© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)