BACKGROUND: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5. OBJECTIVE: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis. METHODS: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.5 or 1 mg) or placebo. After 24 weeks, participants could enter a 2-year, dose-blinded extension. Ozanimod-treated participants continued their assigned dose; placebo participants were re-randomized (1:1) to ozanimod hydrochloride 0.5 or 1 mg (equivalent to ozanimod 0.46 and 0.92 mg). RESULTS: A total of 223 (89.6%) of the 249 participants completed the blinded extension. At 2 years of the extension, the percentage of participants who were gadolinium-enhancing lesion-free ranged from 86.5% to 94.6%. Unadjusted annualized relapse rate during the blinded extension (week 24-end of treatment) was 0.32 for ozanimod hydrochloride 0.5 mg → ozanimod hydrochloride 0.5 mg, 0.18 for ozanimod hydrochloride 1 mg → ozanimod hydrochloride 1 mg, 0.30 for placebo → ozanimod hydrochloride 0.5 mg, and 0.18 for placebo → ozanimod hydrochloride 1 mg. No second-degree or higher atrioventricular block or serious opportunistic infection was reported. CONCLUSION: Ozanimod demonstrated sustained efficacy in participants continuing treatment up to 2 years and reached similar efficacy in participants who switched from placebo; no unexpected safety signals emerged.

Biostatistics Celgene Corporation San Diego CA USA

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Center for Neurology Łódź Poland

Clinical Development Celgene Corporation San Diego CA USA

Department of Neurology and Center for Clinical Neuroscience 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Neurology and Neurological Sciences Beckman Center for Molecular Medicine Stanford University Medical Center Stanford CA USA

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Neurology San Raffaele Scientific Institute Vita Salute San Raffaele University Milan Italy

Division of Neurology and St Michael's Hospital University of Toronto Toronto ON Canada Cemcat Vall d'Hebron University Hospital and Universitat Autònoma de Barcelona Barcelona Spain

Mellen Center for MS Treatment and Research Cleveland Clinic Cleveland OH USA

Neurologic Clinic and Polyclinic University Hospital of Basel and University of Basel Basel Switzerland

NeuroRx Research and Montreal Neurological Institute McGill University Montreal QC Canada

UCSF Weill Institute for Neurosciences and Department of Neurology University of California San Francisco San Francisco CA USA

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