Ozanimod therapy in patients with relapsing multiple sclerosis (MS) has demonstrated a favorable safety/tolerability profile and shown sustained benefits in measures of disease activity, according to the results of a recent study published in the Multiple Sclerosis Journal.
The investigators sought to evaluate the long-term safety and efficacy of ozanimod—an oral sphingosine 1-phosphate receptor 1 and 5 modulator—in patients with relapsing MS. The phase 3, ongoing, single-arm, long-term, observational, open-label extension DAYBREAK trial (NCT02576717) was conducted in individuals who had completed 1 of 4 “parent” ozanimod clinical trials: (1) a 12-week, phase 1 study; (2) the 24-week, phase 2 RADIANCE study, which had an extension period; or (3, 4) 1 of 2 phase 3 trials—the 24-month RADIANCE study or the 12-month SUNBEAM study.
All of the participants from the 4 parent trials were aged between 18 and 55 years with relapsed MS, brain magnetic resonance imaging (MRI) lesions that were consistent with MS, and an Expanded Disability Status Scale score of 0 to 6.0 in the phase 1 trial and 0 to 5.0 in the phase 2 and 3 trials.
DAYBREAK, which commenced in 2015, is being conducted in 25 countries in Europe and North America, as well as in New Zealand and South Africa. A total of 2494 participants were enrolled, with 2055 of them continuing at the data
cut-off. All participants were treated with ozanimod 0.92 mg/day, with a mean duration of ozanimod exposure during the trial of 46.8±11.9 months.
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The adjusted annualized relapse rate (ARR) was 0.103 (95% CI, 0.086 to 0.123). Over 48 months, 71% of the participants remained relapse-free.
The adjusted mean number of new/enlarging T2 lesions per scan and gadolinium-enhancing (GdE) lesions was low and similar across the parent trial treatment subgroups.
Overall, 85.9% (2143 of 2494) of participants experienced at least 1 treatment-emergent adverse event (TEAE). Most were mild or moderate, with severe TEAEs, serious TEAEs, and TEAEs leading to permanent treatment discontinuation reported in 7.6%, 11.9%, and 3.0% of patients, respectively. Nasopharyngitis, headache, and upper respiratory tract infection were the most common TEAEs reported.
Limitations of DAYBREAK include the lack of a control group or blinding. Potential selection bias exists, as patients with less favorable outcomes might have withdrawn from the parent trials.
The researchers concluded that the results of DAYBREAK show that patients with relapsing MS who are “treated with ozanimod 0.92 mg for up to 5 years are consistent with the established safety profile and demonstrate sustained control of disease activity.”
Cree BAC, Selmaj KW, Steinman L, et al. 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. Mult Scler. Published online June 28, 2022. doi:10.1177/13524585221102584