Blood-based measurement of neurofilament light chain (NfL), which has been suggested as a potential biomarker in hereditary transthyretin amyloidosis (hATTR), was successfully used as a surrogate endpoint in a neurology therapeutic trial evaluating tofersen in adults with amyotrophic lateral sclerosis (ALS).

The strong surrogate biomarker data was critical for the US Food and Drug Administration’s (FDA) decision to approve tofersen through its Accelerated Approval Program. The FDA Advisory Committee agreed unanimously that the “reduction in plasma NfL concentration in tofersen-treated patients is reasonably likely to predict clinical benefit of tofersen for treatment of patients with SOD1-ALS [superoxide dismutase 1 amyotrophic lateral sclerosis].”

FDA’s accelerated approval of tofersen highlights the potential added value of including blood-based NfL measurements in other therapeutic trial designs.

“Blood-based NfL measurements are materially advancing and accelerating therapeutics development for, and clinical management of, patients with neurodegenerative diseases, including Alzheimer’s, spinal muscular atrophy, hATTR, and multiple sclerosis,” Masoud Toloue, CEO at Quanterix, said in a press release.

Read more about hATTR diagnosis

“On the strength of hundreds of published studies in recent years, blood NfL has gained broad acceptance as a biomarker of neuro-axonal damage which is a common feature of these diseases. We are pleased to see another validating proof point on how this biomarker can be accelerative in neurodegeneration therapeutics development. We are hopeful that the approval of tofersen will provide some relief to sufferers of the relentless progression of SOD1-ALS.”

“An important advance stemming from the tofersen approval is a demonstration of the potential of NfL as a potential surrogate biomarker that can serve as a leading indicator of drug efficacy for some investigational therapies in neurodegenerative disorders,” said Merit Cudkowicz, MD, MSc, chair of neurology at Mass General.

The results of the phase 3 trial showed that tofersen treatment decreased plasma levels of NfL by 40% to 50% over a 6-month period.

NfL has been extensively studied in several neurodegenerative diseases, including hATTR.


FDA accelerated approval of tofersen highlights importance of blood neurofilament light chain as surrogate endpoint in neurology therapeutic trials. News release. Quanterix Corporation; April 25, 2023.