Characterization of Neurological Biomarkers in Patients with Early Relapsing Multiple Sclerosis and Comparison to Healthy Controls: Year 1 Interim Analysis of the ENLIGHTEN Study of Ozanimod
Sarah A. Morrow1, Lauren P. Shapiro2, Aditi Basu Bal2, Jon V. Riolo2, Sarah Harris2
1London Health Sciences Centre, University Hospital, University of Western Ontario, London, Ontario, Canada, and Department of Clinical Neurological Sciences, Hotchkiss Brain Institute, University of Calgary, 2Bristol Myers Squibb
Objective:
Evaluate the effect of 1 year of ozanimod on biomarkers of axonal and astrocytic damage in patients with early relapsing multiple sclerosis (RMS) and compare biomarker concentrations in patients with RMS vs healthy controls.
Background:
Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and Tau are markers of astrocytic and neuronal damage and serve as biomarkers of RMS disease activity and progression.
Design/Methods:
ENLIGHTEN (NCT04140305) is an ongoing, multicenter, single-arm, open-label study of ozanimod 0.92 mg in adults with early RMS (≤1 prior disease-modifying therapy; Expanded Disability Status Scale score of ≤3.5; ≤5 years since RMS diagnosis). GFAP, NfL, and Tau concentrations were assessed at baseline and 12 months (Quanterix Neuro 4-plex assay) in plasma samples from ENLIGHTEN participants and commercial samples from healthy volunteers. Spearman correlation analysis, Wilcoxon test, and Mann Whitney U test were used to evaluate and compare concentrations. Data cutoff: 2/7/2024.
Results:
Of 163 patients with RMS and biomarker data, 79% were female; 86% White; and 68% untreated. Age and gender were not significantly different between patients with RMS and 210 healthy controls. Baseline NfL levels were significantly higher in untreated than previously treated patients with RMS (P=0.01); however, baseline GFAP and Tau levels did not differ between untreated and treated patients. Baseline NfL, GFAP, and Tau levels were higher in patients with RMS than in healthy controls (P<0.0001). After 1 year of ozanimod, NfL, GFAP, and Tau levels were all reduced from baseline (P<0.0001, P=0.006, P=0.01, respectively), and NfL levels in patients with RMS were no different than those of controls (mean 9.3 vs 9.7 pg/mL respectively; P=1.0).
Conclusions:
In ENLIGHTEN patients, early treatment with ozanimod significantly decreased markers of axonal and neuronal damage at 1 year compared with baseline and normalized NfL levels to those of healthy controls, indicating slowed disease activity.
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