Quanterix Corporation, a company fueling scientific discovery and breakthrough diagnostics through ultrasensitive biomarker detection, announced that blood-based NfL measurements provided compelling support for the FDA’s accelerated approval of tofersen for treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS), a devastating rare genetic form of ALS. This is the first known case in which a blood biomarker was successfully used as a surrogate endpoint for a neurology therapeutic trial to gain accelerated approval, highlighting the potential for other therapeutic trial designs to benefit from including blood NfL measurements.
Tofersen is designed to reduce the overproduction of SOD1 protein in SOD1-ALS patients. In the Phase III VALOR trial, the drug did not significantly slow patients’ clinical decline. However, there were positive trends in the data, and open label extension results have since shown evidence of clinical benefits along with highly significant reductions of secondary endpoint biomarkers in favor of a positive treatment effect. This data supported an extended FDA review of tofersen’s new drug application under the accelerated pathway leading to its recent announcement of approval.
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Critical to the approval were plasma NfL trends, with the FDA Advisory Committee voting unanimously that the “reduction in plasma neurofilament light chain (NfL) concentration in tofersen-treated patients is reasonably likely to predict clinical benefit of tofersen for treatment of patients with SOD1-ALS.” Tofersen was found to lower plasma NfL levels 40-50 percent over a six-month period.
The FDA’s decision to approve tofersen through its Accelerated Approval Program focused on strong surrogate biomarker data, adding momentum to the use of biomarkers in predicting disease severity and clinical benefit in neurodegenerative diseases. NfL, in particular, has been extensively studied in different neurodegenerative diseases, including Alzheimer’s, spinal muscular atrophy, hereditary transthyretin-mediated amyloidosis, and multiple sclerosis.
“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, M.D., M.Sc., Director of the Sean M. Healey & AMG Center for ALS and Chair of Neurology at Mass General. “The acceptance of NfL as a valid biomarker for accelerated therapeutics in ALS is a major advance. I fully expect that more biomarkers like NfL will be discovered in ALS. This is a very exciting and hopeful time in ALS therapeutics.”
SOURCE: Businesswire