Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Final analysis of the DAYBREAK open-label extension trial

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.