Long-term Efficacy of the Sphingosine 1-Phosphate Receptor Modulator Ozanimod by Age Category in Patients with Relapsing Multiple Sclerosis: Final Results from Two Phase 3 Trials and an Open-label Extension Trial
Lawrence Steinman1, Krzysztof Selmaj2, Giancarlo Comi3, Amit Bar-Or4, Douglas Arnold5, Hans-Peter Hartung6, Xavier Montalban7, Eva Havrdova8, James Sheffield9, Chun-Yen Cheng9, Jennifer Reardon9, Jon Riolo9, Erik Deboer9, Ludwig Kappos10, Jeffrey Cohen11, Bruce Cree12
1Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, 2Center for Neurology, Łódź, Poland, and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 3Vita-Salute San Raffaele University and Casa di Cura del Policlinico, Milan, Italy, 4Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 5NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada, 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Australia; Department of Neurology, Medical University of Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 7Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain, 8Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic, 9Bristol Myers Squibb, Princeton, New Jersey, 10Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 11Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, 12Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California
Objective:
To evaluate long-term efficacy of ozanimod by age category.
Background:
Ozanimod was associated with lower adjusted annualized relapse rate (ARR) and fewer gadolinium-enhancing (GdE) lesions and new/enlarging T2 lesions compared with interferon (IFN) β-1a in patients with relapsing multiple sclerosis (RMS) in phase 3 randomized trials (SUNBEAM/RADIANCE). Patients who completed phase 1‒3 ozanimod RMS trials were eligible for an open-label extension (OLE) trial (DAYBREAK).
Design/Methods:
In SUNBEAM/RADIANCE (“parent trials”), adults (18‒55y) with RMS received oral ozanimod 0.46 or 0.92 mg/d or intramuscular IFN β-1a 30 µg/wk for ≥12 (SUNBEAM, NCT02294058) or 24 (RADIANCE, NCT02047734) months. In the OLE (DAYBREAK, NCT02576717), they received ozanimod 0.92 mg/d. This ad hoc analysis assessed clinical and radiologic outcomes by age (≤25, >25 to ≤35, >35 to ≤49, or ≥50y) at parent trial baseline in patients who received ozanimod 0.92 mg in both the parent trials and OLE (database lock: April 7, 2023).
Results:
Of 2257 patients from SUNBEAM/RADIANCE enrolled in the OLE, 760 received continuous ozanimod 0.92 mg (≤25y, n=118; >25 to ≤35y, n=268; >35 to ≤49y, n=312; and ≥50y, n=62 at parent trial baseline). Regardless of age category, adjusted ARR was <0.2 in the parent trials and OLE. Adjusted mean number of GdE lesions remained lower than at parent trial baseline over 7–8 years of ozanimod treatment, regardless of age category. Adjusted mean number of new/enlarging T2 lesions per scan relative to OLE baseline generally remained stable throughout the OLE regardless of age category. Patients ≥50y had a numerically lower adjusted ARR and fewer GdE lesions and new/enlarging T2 lesions per scan than those ≤25y.
Conclusions:
Regardless of age category, clinical and radiologic measures of disease activity remained stable or improved in ozanimod-treated patients with RMS over 7‒8 years of continuous treatment.