Associations Between NfL Concentrations and Cognitive and Radiologic Outcomes Revealed in Study of Individuals with RMS Treated with Zeposia

Research presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025 demonstrated that neurofilament light chain (NfL) may be a useful biomarker for both cognitive and radiologic outcomes in early relapsing multiple sclerosis (RMS). The findings result from 1-year interim data from the ongoing, 3-year, phase 3, open-label ENLIGHTEN clinical study (NCT04140305), which will evaluate changes from baseline in people with early RMS treated with Zeposia (ozanimod; Bristol Myers Squibb, Princeton, NJ), a once-daily oral agonist of the sphingosine-1-phosphate receptor (S1PR).

ENLIGHTEN enrolled an estimated 250 adults with early RMS who will receive treatment with Zeposia .92 mg once daily for up to 3 years. In the interim analysis, participants were assessed at baseline and annually for plasma NfL concentrations, cognitive outcomes, and radiologic outcomes based on MRI imaging. The primary endpoint of the study is the proportion of participants with an increase from baseline of ≥4 points or 10% in raw score on the Symbol Digit Modalities Test (SDMT). For this interim analysis, researchers assessed the statistical relationships between plasma NfL concentrations and cognitive and radiologic outcomes.

For all participants with relevant data (n=175) there was a mean (standard deviation [SD]) reduction in NfL levels from 14.6 (12.2) pg/mL at baseline to 9.3 (5.8) pg/mL after 1 year of treatment with Zeposia. In terms of cognitive outcomes (n=161), lower NfL concentrations were associated with higher scores on the SDMT, California Verbal Learning Test–Second Edition (CVLT-II), and Brief Visuospatial Memory Test–Revised (BVMT-R). For radiological outcomes (n=162), lower NfL concentrations were associated with reduced counts and volumes of gadolinium-enhancing, T1, and T2 lesions and with greater whole brain, cortical gray matter, and thalamic volumes.