Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.
Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice.
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肌萎缩侧索硬化症神经丝轻链的生物标志物鉴定：理论与实践。
DOI：
10.1002/ana.26860
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发表时间：
2024
影响因子：
11.2
通讯作者：
Wuu,Joanne
中科院分区：
文献类型：
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作者：
Benatar,Michael;Ostrow,LyleW;Lewcock,JosephW;Bennett,Frank;Shefner,Jeremy;Bowser,Robert;Larkin,Paul;Bruijn,Lucie;Wuu,Joanne
目的：探讨神经丝轻链（NfL）作为一种生物标志物在肌萎缩性侧索硬化症（ALS）治疗开发中的应用，是否可以通过获得美国食品和药物管理局（fda）的正式使用资格来增强。方法在学术界、产业界和患者权益团体代表中进行共识讨论。结果：大量科学证据支持将NfL作为广泛ALS人群的预后、反应和潜在安全性生物标志物，以及sod1致病变异携带者亚群的风险/易感性生物标志物。尽管NfL尚未被正式批准用于上述任何一种情况，但美国食品和药物管理局（fda）已经加速批准了一种降低SOD1的反义寡核苷酸，部分原因是认识到NfL的降低有可能预测临床获益。越来越多的将NfL纳入ALS治疗发展计划提供了证据，证明其作为预后、反应、风险/易感性和/或安全性生物标志物的效用已经被社会广泛接受。美国食品和药物管理局（fda）愿意根据严格的同行评审数据（缺乏正式资格）做出监管决定，这使我们得出结论，尽管有一些好处，但正式资格对于正在进行和未来使用NfL作为辅助ALS治疗发展的工具并不是必不可少的。尽管在不同的疾病和使用背景下，支持和反对寻求NfL生物标志物资格的考虑无疑会有所不同，但已发表数据的稳健性和ALS社区的仔细审议可能为其他疾病社区解决相同问题提供有价值的见解。Ann neurol 2024；95:211 - 216
ObjectiveTo 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.MethodsConsensus discussion among academic, industry, and patient advocacy group representatives.ResultsA 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 ofSOD1pathogenic 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.InterpretationThe 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