Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial

Abstract

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.

OzEAN Study to Collect Real-World Evidence of Persistent Use, Effectiveness, and Safety of Ozanimod Over 5 Years in Patients With Relapsing-Remitting Multiple Sclerosis in Germany

“…In summary, this is the first long-term, real-world study of ozanimod in patients with RRMS. These data will add to the safety and efficacy profile of ozanimod previously demonstrated in the phase 3 trials (6,7) and the ongoing open-label extension study of phase 1-3 trials (DAYBREAK) (27) in patients with relapsing MS, and they will provide new information on endpoints not previously evaluated in ozanimod clinical trials. To our knowledge, this is the first non-interventional study utilizing a patient portal, which is expected to facilitate study participation and compliance, provide valuable information on PROs, and draw a high-resolution picture of the course of disease independent of study visits in a convenient way (41).…”

“…OzEAN is an ongoing study to evaluate ozanimod treatment for RRMS in real-world clinical practice in Germany, with a large sample size, sophisticated methodology, and complex design involving endpoints related to multiple MS symptoms and functional consequences. The findings from this real-world evidence study will provide an important complement to the efficacy and safety results from highly structured randomized controlled trials ( 26 ), including phase 3 clinical trials ( 6 , 7 ) and the ongoing open-label extension study of phase 1–3 trials (DAYBREAK) ( 27 ).…”

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

“…Participants with RMS who completed any of the four ozanimod phase 1, 2, or 3 "parent" trials were eligible to enter a single-arm, open-label, phase 3 trial of oral ozanimod 0.92 mg (DAYBREAK, ClinicalTrials.gov: NCT02576717; EudraCT: 2015-002500-91). 16 The phase 1 trial was a randomized, 12-week, open-label pharmacokinetic/pharmacodynamic study of oral ozanimod 0.46 or 0.92 mg/d. 4 The phase 2 study was a randomized, double-blind, 24-week, placebo-controlled study of oral ozanimod 0.46 or 0.92 mg/d, followed by a 24-month dose-blinded extension where all participants received ozanimod.…”

“…[5][6][7][8][9][10][11][12][13][14][15] The ability of ozanimod-treated participants to mount a response to SARS-CoV-2 infection was observed in an interim analysis of the DAYBREAK open-label extension trial, where COVID-19-related adverse events (AEs) were largely nonserious, and most participants recovered without sequelae. 16 There is insufficient evidence available regarding the impact of ozanimod on the serologic response to SARS-CoV-2 vaccination and/or infection. Given that most patients with MS are willing to be vaccinated against SARS-CoV-2, 17 the primary aim of this retrospective analysis was to investigate the serologic response to SARS-CoV-2 vaccination and clinical outcomes of COVID-19 in vaccinated ozanimod-treated participants with RMS from the DAYBREAK trial, with a secondary aim of determining the serologic response to infection.…”

Aktualisierung der „Living Guideline“ Colitis ulcerosa 2022

“…Die Wirksamkeit von Ozanimod bei CED wurde in der TRUE-NORTH-Studie untersucht [3]. Real-World-Daten zum Einsatz von Ozanimod bei Colitis ulcerosa liegen bisher noch nicht vor, lediglich die Langzeitdaten der TOUCHSTONE Phase-2-Studie und Daten in der Indikation Multiple Sklerose, die in einem Zeitraum über 5 Jahre keine relevanten Sicherheitsprobleme identifizierten, wenngleich der Einsatz von Ozanimod häufig mit einer Lymphopenie assoziiert ist [4,5].…”