BACKGROUND: Ozanimod, a selective, oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for adults with relapsing forms of multiple sclerosis (RMS). OBJECTIVE: To characterize the long-term safety and efficacy of ozanimod. METHODS: Participants were eligible for an open-label extension study of ozanimod 0.92 mg/d (DAYBREAK) if they completed a phase 1-3 RMS ozanimod 'parent' trial. DAYBREAK began 16 October 2015, and ended 5 January 2023. RESULTS: DAYBREAK included 2494 participants with a mean of 60.9 (range 0.03‒81.5) months of ozanimod exposure. During DAYBREAK, 2219 participants (89.0%) had treatment-emergent adverse events (TEAEs), 381 (15.3%) had a serious TEAE and 98 (3.9%) discontinued treatment due to TEAEs. Serious infections (4.3%), herpes zoster infections (2.0%), confirmed macular oedema cases (0.2%), and cardiac TEAEs (4.1 %) were infrequent. Adjusted annualized relapse rate was 0.098 (95% confidence interval, 0.082‒0.117). In total, 69.1% of participants remained relapse-free and 84.8% were free from 6-month confirmed disability progression at DAYBREAK completion. Adjusted mean numbers of new/enlarging T2 lesions/scan and gadolinium-enhancing lesions were low and remained relatively stable. CONCLUSIONS: Long-term ozanimod treatment had a favourable safety and tolerability profile and provided sustained control of clinical and MRI disease activity in participants with RMS.Registries:ClinicalTrials.gov ID: NCT02576717; EudraCT: 2015-002500-91.

Beckman Center for Molecular Medicine Stanford University Medical Center Stanford CA USA

Brain and Mind Centre The University of Sydney Camperdown NSW Australia

Bristol Myers Squibb Princeton NJ USA

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

Center for Neurology Łódź Poland

Collegium Medicum University of Warmia and Mazury Olsztyn Poland

Department of Neurology and Center for Clinical Neuroscience 1st Medical Faculty and General University Hospital Prague Czech Republic

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

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacký University Olomouc Olomouc Czech Republic

Mellen Center for Multiple Sclerosis Treatment and Research Cleveland Clinic Cleveland OH USA

NeuroRx Research and Montréal Neurological Institute McGill University Montreal QC Canada

Research Center for Clinical Neuroimmunology and Neuroscience Basel Departments of Head Organs 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 Igea Milan Italy

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

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ClinicalTrials.gov
NCT02576717