ENLIGHTEN (NCT04140305) is a prospective, multicenter, open-label study of ozanimod 0.92mg. The proportion of participants with an increase in Symbol Digit Modalities Test [SDMT] score of ≥4 points or ≥10% from baseline was assessed at 1 year, along with clinical and radiologic endpoints. Treatment-emergent adverse events (TEAEs) were assessed from study start (1/16/2020) through 2/14/2023.

Participants (N=185) were mostly female (78.4%), White (85.9%), and naive to disease-modifying therapy (72.4%). Mean (standard deviation [SD]) age at baseline was 39.5 (10.7) years, time since MS symptom onset was 4.1 (5.5) years, time since diagnosis was 1.1 (1.2) years, and number of relapses in the prior year was 0.8 (0.8); median Expanded Disability Status Scale score was 2.0 (range 0–4). At baseline, mean (SD) SDMT score was 53.9 (11.4) and T2 lesion count was 22.4 (16.9). After 1 year of ozanimod, 55/116 (47.4%) had ≥4-point or ≥10% SDMT improvement. Annualized relapse rate was 0.2 (95% CI, 0.1?0.4). At 1 year, adjusted mean (95% CI) new/enlarging T2 lesion count was 0.4 (0.3?0.6), and an estimated 91.9% (95% CI, 84.2?96.0) of 100 patients with MRI data were gadolinium-enhancing lesion–free. TEAEs occurred in 122 (65.9%) patients, most commonly COVID-19 (17.3%), headache (10.3%), fatigue (9.2%), urinary tract infection (6.5%), sinusitis (5.9%), nasopharyngitis (5.4%), muscle weakness (5.4%), and hypertension (5.4%).