Safety and Efficacy of Ozanimod in Patients with Early Relapsing Multiple Sclerosis: 1-year Analysis of the ENLIGHTEN Study
Robert Naismith1, Robert Zivadinov2, Sarah Morrow3, Ann Bass4, Ahmed Obeidat5, Emily Riser6, Sibyl Wray7, Massimiliano Cristofanilli8, Jon Riolo8, Andrew Thorpe8, Burhan Chaudhry8, Kamran Mohiuddin8, Chun-Yen Cheng8, John DeLuca9
1Washington University School of Medicine, St Louis, Missouri, 2Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, 3London Health Sciences Centre, University Hospital, University of Western Ontario, London, Ontario, Canada, and Department of Clinical Neurological Sciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, 4Neurology Center of San Antonio, San Antonio, Texas, 5Department of Neurology, The Medical College of Wisconsin, Milwaukee, Wisconsin, 6Alabama Neurology Associates, Birmingham, Alabama, 7Hope Neurology MS Center, Knoxville, Tennessee, 8Bristol Myers Squibb, Princeton, New Jersey, 9Kessler Foundation, West Orange, New Jersey, and Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark, New Jersey
Objective:
This ad hoc analysis describes the efficacy and safety profile of ozanimod over 1 year.
Background:
ENLIGHTEN is an ongoing 3-year study of ozanimod in adults with early relapsing multiple sclerosis (RMS).
Design/Methods:
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.
Results:
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%).
Conclusions:
Nearly half of this population with early RMS had ≥4-point or ≥10% improvement in SDMT score after 1 year of ozanimod treatment. Clinical and radiologic improvements were observed. COVID-19 was the most frequent TEAE during ENLIGHTEN, which began in January 2020. Other common TEAEs were largely consistent with those previously reported in ozanimod trials.