In this post hoc analysis, NfL levels were measured in baseline serum samples from patients with RMS in two phase 3 trials (SUNBEAM and RADIANCE) that compared the oral sphingosine 1-phosphate receptor-1 and -5 modulator ozanimod HCl 0.5 or 1 mg/d with intramuscular interferon β-1a 30 µg/wk. NfL levels were analyzed in the overall study populations and categorically based on the number of gadolinium-enhancing (GdE) and T2 MRI lesions and on relapse rates. 

NfL levels were measured in 1,313 and 1,346 patients from RADIANCE and SUNBEAM respectively; mean (SD) baseline NfL levels were 18.6 (19.8) pg/mL in RADIANCE and 19.6 (16.1) pg/mL in SUNBEAM. In both studies, baseline NfL levels were higher in patients with more GdE and T2 lesions and increased incrementally with escalating lesion counts. No relationship was found between baseline NfL levels and number of relapses reported in the 12 or 24 months prior to initiation of treatment in either trial; however, patients who subsequently relapsed while on study treatment had higher baseline NfL levels than those who did not.

Based on data from the ozanimod phase 3 studies, these findings suggest that NfL levels may be used as a marker of acute disease in RMS, correlate with the number of GdE and T2 MRI lesions, and may be predictive of future relapses.