Neurofilament Light Chains as a Marker of Concurrent and Future Active Disease in Relapsing Multiple Sclerosis: An Analysis of Baseline Data From the Phase 3 Ozanimod Clinical Trials (S56.006)

Objective: To explore the relationship between plasma neurofilament light chain (NfL) levels and relapsing multiple sclerosis (RMS) disease activity in phase 3 ozanimod trials. Background: NfL is released into serum/plasma and cerebrospinal fluid following axonal/neuronal injury and may serve as a biomarker for ongoing neurologic damage. Design/Methods: 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. Results: 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. Conclusions: 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. Disclosure: Dr. Harris has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene Corporation. Dr. Comi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer, Biogen, Merck Serono, Novartis, Sanofi, Serono Symposia International Foundation, and Teva. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis. Dr. Steinman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene, Merck, Coherus, and Atreca. Dr. Steinman has received compensation for serving on the Board of Directors of Atreca and Tolerion. Dr. Steinman has received royalty, license fees, or contractual rights payments from Tolerion. Dr. Steinman has received research support from Coherus and Celgene. Dr. Sheffield has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene Corporation. Dr. Silva has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene Corporation. Dr. Southworth has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene, GSk, Astrazeneca, Ardea, University of Manchester, University of Lancaster, Clarostat Ltd, Alphamedstat Ltd, Stone Biostatistics Ltd, and Allecra. Dr. Kappos’ institution has received compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva and Vianex, and license fees for Neurostatus-UHB products. Dr. Kappos’ institution has received research support from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union, and Roche Research Foundations.