Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.
Ann Neurol
; 95(2): 211-216, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38110839
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;95211-216.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esclerosis Amiotrófica Lateral
Límite:
Humans
Idioma:
En
Revista:
Ann Neurol
/
Ann. neurol
/
Annals of neurology
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos