FDA Grants Breakthrough Device Designation to Simoa Neurofilament Light Chain Test for Multiple Sclerosis

Mark Freedman, MD, MSc, HBSc, CSPQ, FANA, FAAN, FRCPC

The FDA has granted breakthrough device designation to Quanterix’s Simoa neurofilament light (NfL) chain test as a prognostic aid in assessing the risk of disease activity in patients with relapsing-remitting multiple sclerosis (MS).¹

Used to quantitatively measure NfL in human serum, plasma, and cerebrospinal fluid, the program is designed to enable accelerated development, assessment, and review processes, with the intention to provide patients with more timely access to breakthrough technologies or devices. In recent weeks, the Simoa NfL assay was referenced in at least 20 studies presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, April 2-7, in Seattle Washington.

"There has been an ever-growing body of research with the Simoa NfL blood test supporting NfL as a reliable biomarker for MS disease activity prognosis and treatment response monitoring,” Mark S. Freedman, MD, MSc, HBSc, CSPQ, FANA, FAAN, FRCPC, professor of neurology, and director, Multiple Sclerosis Research, Ottowa Hospital, said in a statement.¹ "The FDA’s grant of breakthrough device designation for this test has the potential to help the multiple sclerosis community further advance the optimal use of NfL measurements in both research and clinical practice aimed at more effective therapeutic management of the disease for the millions of patients suffering from the condition."

Serum NfL is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs, but to prognosticate disease course in patients with MS. Recently, data from an international, large-scale study that helped establish a new method for clinicians to identify and interpret elevated values of serum NfL in patients with MS were published by Pascal Benkert, PhD, and colleagues. The study aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive references values corrected for age and body mass index. Investigators compared the association of serum NfL z-scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capability.²

READ MORE: Burden of Direct, Indirect Costs of Multiple Sclerosis Are Underreported, Study Suggests

A total of 10,133 blood samples from 5390 patients with MS from the Swiss Multiple Sclerosis Cohort (SMSC) were included. At the conclusion of the analysis, serum NfL percentiles and z-scores indicated a gradually increased risk for future acute and chronic disability worsening. A serum NfL z-score above 1.5 was associated with an increased risk of future clinical or MRI disease activity in all patients with MS (odds ratio [oR], 3.15; 95% CI, 2.35-4.23; P <.0001) and in individuals with no evidence of disease activity (OR, 2.66; 95% CI, 1.08-6.55; P = .034).²

Benkert et al then used that reference database to test the suitability of serum NfL as an end point for group-level comparison of effectiveness across disease-modifying therapies. At the group-level, the longitudinal course of serum NfL z-score values of those with MS from the SMSC decreased in comparison to the control group with use of monoclonal antibodies (alemtuzumab, natalizumab, ocrelizumab, and rituximab), and, to a lesser extent, oral therapies (dimethyl fumarate, fingolimod, siponimod, and teriflunomide).

"For the more than 2 million people suffering from MS worldwide, there’s an important need for more informed and effective treatment options,” Kevin Hrusovsky, chairman and chief executive officer, Quanterix, and founder, Powering Presicion Health, said in a statement.¹ "Obtaining FDA breakthrough device designation for our plasma NfL MS test was a key objective for 2022. We are pleased to have the opportunity to work with the FDA to help advance the Quanterix Simoa NfL test towards regulatory approval."

This is the second test from Quanterix to receive breakthrough device status. In October 2021, the FDA granted the same designation to the Simoa phospho-tau 181 (p-tau181) blood test, an aid in the diagnostic evaluation of Alzheimer disease. This semiquantitative immunoassay is intended to measure p-tau181 concentration in human serum and plasma using the Quantrix HD-X immunoassay system. The test is not intended as a stand-alone diagnostic assay and test results are interpreted in conjunction with other diagnostic tools to establish a final diagnosis.³

REFERENCES
1. Quanterix granted breakthrough device designation from the FDA for NfL test for multiple sclerosis. News release. Quanterix. April 22, 2022. Accessed April 22, 2022. https://www.businesswire.com/news/home/20220421006165/en/Quanterix-Granted-Breakthrough-Device-Designation-from-U.S.-FDA-for-NfL-Test-for-Multiple-Sclerosis

2. Benkert P, Meier S, Schaedelin S, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modeling and validation study. Lancet Neuro. 2022;21(3):246-257

3. Quanterix granted breakthrough device designation from US FDA for blood-based PTau-181 assay for Alzheimer disease. News release. Quanterix. October 18, 2021. Accessed April 22, 2022. https://www.quanterix.com/press-releases/quanterix-granted-breakthrough-device-designation-from-u-s-fda-for-blood-based-ptau-181-assay-for-alzheimers-disease/