For patients with multiple sclerosis (MS), ozanimod provides continued control of disease activity and a consistent safety profile, according to interim results from the DAYBREAK open-label extension study.
Bruce Cree, MD, PhD, and colleagues conducted the study to determine the interim efficacy and safety of ozanimod over an extended period. The open-label extension phase included the COVID-19 pandemic, with results gathered through February 2, 2021; the researchers also examined COVID-19 infections in patients treated with ozanimod. Patients with relapsing MS were treated with ozanimod 0.92 mg/day. Safety outcomes were recorded as treatment-emergent adverse events (TEAEs), efficacy outcomes of annualized relapse rate (ARR), and the adjusted mean numbers of new/enlarging T2 and gadolinium-enhancing lesions on brain MRI. MRI brain lesions were reported for patients entering the open-label extension from an active-controlled phase III trial. COVID-19 cases in DAYBREAK participants between November 1, 2019 and May 10, 2021 were determined based on reported adverse event preferred terms related to coronavirus infection or positive coronavirus test.
Among 2,639 eligible patients, 2,494 patients enrolled in DAYBREAK. The mean (range) ozanimod exposure was 46.8 (0.03-62.7) months (9,725.6 patient-years) in the open-label extension. Ozanimod provided consistent efficacy, with a low ARR (adjusted ARR, 0.103 [95% CI, 0.086-0.123]). At month 48 in the open-label extension, the adjusted mean numbers of new/enlarging T2 and gadolinium-enhancing lesions relative to DAYBREAK baseline were low and similar across parent trial treatment groups (T2: 0.85-1.03; gadolinium-enhancing lesions: 0.06-0.12). The investigators reported TEAEs in 2,143 patients (85.9%), which were similar to those in the parent trials; 298 patients (11.9%) had a serious TEAE, and 75 (3.0%) stopped treatment as a result of TEAEs.
COVID-19 Impact & Overall Risk-Benefit Profile
As of May 2021, 190 of 2,181 patients (8.7%) had confirmed (N=160) or suspected (N=30) COVID-19. The researchers reported three deaths, one from active COVID-19 infection/pulmonary embolism and two from complications after COVID-19, including acute respiratory failure and a lung abscess after pneumonia. The majority of COVID-19 cases (N=176/190; 92.6%) were not deemed to be serious. Additionally, 119 patients (62.6%) with COVID-19 continued treatment with ozanimod without interruption, of whom 113 recovered without sequelae. No patients with COVID-19 permanently discontinued ozanimod.
The interim results from the DAYBREAK trial, in which patients were treated for up to 62.7 months, were consistent with the known safety profile of ozanimod and indicated that the agent provided consistent control of disease activity, according to Dr. Cree and colleagues. They also reported that the risk-benefit profile of ozanimod remains the same, as most COVID-19 infections were considered not to be serious and resolved without an ozanimod treatment interruption.