BACKGROUND: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for treatment of relapsing forms of MS. OBJECTIVE: To characterize long-term safety and efficacy of ozanimod. METHODS: Patients with relapsing MS who completed a phase 1‒3 ozanimod trial were eligible for an open-label extension study (DAYBREAK) of ozanimod 0.92 mg/d. DAYBREAK began 16 October 2015; cutoff for this interim analysis was 2 February 2021. RESULTS: This analysis included 2494 participants with mean 46.8 (SD 11.9; range 0.033‒62.7) months of ozanimod exposure in DAYBREAK. During DAYBREAK, 2143 patients (85.9%) had treatment-emergent adverse events (TEAEs; similar in nature to those in the parent trials), 298 (11.9%) had a serious TEAE, and 75 (3.0%) discontinued treatment due to TEAEs. Serious infections (2.8%), herpes zoster infections (1.7%), confirmed macular edema cases (0.2%), and cardiac TEAEs (2.8%) were infrequent. Adjusted annualized relapse rate was 0.103 (95% confidence interval, 0.086‒0.123). Over 48 months, 71% of patients remained relapse free. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and similar across parent trial treatment subgroups. CONCLUSIONS: This long-term extension of ozanimod trials confirmed a favorable safety/tolerability profile and sustained benefit on clinical and magnetic resonance imaging measures of disease activity.

Bristol Myers Squibb Princeton NJ 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 and Collegium Medicum Department of Neurology University of Warmia and Mazury in Olsztyn Olsztyn Poland

Department of Neurology and Center for Clinical Neuroscience 1st Medical Faculty 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 Brain and Mind Centre The University of Sydney Sydney Australia Department of Neurology Medical University of Vienna Vienna Austria Department of Neurology Palacky University Olomouc Olomouc Czech Republic

Department of Neurology Neuroimmunology Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Barcelona Spain

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

NeuroRx Research and Montréal Neurological Institute McGill University Montréal QC Canada

Research Center for Clinical Neuroimmunology and Neuroscience Basel Departments of Head Spine and Neuromedicine Clinical Research Biomedicine and Biomedical Engineering University Hospital and University of Basel Basel Switzerland

Vita Salute San Raffaele University and Casa di Cura del Policlinico Milan Italy

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

Mult Scler. 2022 Nov 30:13524585221138507. doi: 10.1177/13524585221138507. PubMed

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Bioavailable central nervous system disease-modifying therapies for multiple sclerosis

SARS-CoV-2 vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis