Abstract: Long-Term Efficacy and Safety, Including COVID-19 Outcomes, Among Ozanimod-Treated Patients with Relapsing Multiple Sclerosis in the Daybreak Open-Label Extension Trial (2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers)

DMT14
Long-Term Efficacy and Safety, Including COVID-19 Outcomes, Among Ozanimod-Treated Patients with Relapsing Multiple Sclerosis in the Daybreak Open-Label Extension Trial

Thursday, June 2, 2022

Prince George's Exhibit Hall (Gaylord National Resort & Convention Center)

Bruce A.C. Cree, MD , Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA

Krzysztof W. Selmaj, MD , Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland

Lawrence Steinman, MD , Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA

Giancarlo Comi, MD , Vita-Salute San Raffaele University and Casa di Cura del Policlinico, Milan, Italy

Amit Bar-Or, MD , Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, and NeuroRx Research, Montreal, QC, Canada

Hans-Peter Hartung, MD , Heinrich-Heine University, Düsseldorf, Germany, Brain and Mind Center, University of Sydney, Sydney, NSW, Australia, Medical University of Vienna, Vienna, Austria, Palacky University Olomouc, Olomouc, Czech Republic

Xavier Montalban, MD, PhD , Department of Neurology-Neuroimmunology, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d’Hebron, Barcelona, Spain

Eva K Havrdova, MD, PhD , Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic

James K. Sheffield, MD, MBA, MS , Bristol Myers Squibb, Princeton, NJ

Neil Minton, MD FFPM , Bristol Myers Squibb, Princeton, NJ

Chun-Yen Cheng, PhD , Bristol Myers Squibb, Princeton, NJ

Diego Silva, MD , Bristol Myers Squibb, Princeton, NJ

Ludwig Kappos, MD , Research Center for Clinical Neuroimmunology and Neuroscience, Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland

Jeffrey A Cohen, MD , Mellen MS Center, Cleveland Clinic, Cleveland, OH

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Background: Four clinical trials of ozanimod were completed in patients with relapsing multiple sclerosis (RMS). DAYBREAK is an ongoing open-label extension (OLE) study that enrolled patients from these parent trials.

Objectives: To report interim efficacy and safety data, including COVID-19 outcomes, during extended exposure to ozanimod among patients in DAYBREAK.

Methods: Patients with RMS who completed a phase 1, 2, or 3 ozanimod parent trial were eligible to enroll in DAYBREAK (NCT02576717), where they received ozanimod 0.92 mg/d. Safety outcomes (treatment-emergent adverse events [TEAEs]) and efficacy outcomes of annualized relapse rate (ARR) and adjusted mean number of new/enlarging T2 and gadolinium-enhancing (GdE) lesions on brain MRI (all calculated via negative binomial regression) were evaluated through February 2, 2021. MRI brain lesions were reported for patients who entered the OLE from an active-controlled phase 3 trial. COVID-19 cases occurring in DAYBREAK between November 1, 2019 and May 10, 2021 were identified based on reported adverse event preferred terms related to coronavirus infection or coronavirus test positive.

Results: Of 2639 eligible patients, 2494 enrolled in DAYBREAK. With a mean (range) ozanimod exposure of 46.8 (0.03–62.7) months (9725.6 patient-years) in the OLE, ozanimod demonstrated sustained efficacy with a low adjusted ARR (0.103 [95% CI, 0.086‒0.123]). At OLE month 48, the adjusted mean numbers of new/enlarging T2 and GdE lesions relative to DAYBREAK baseline were low and similar across parent trial treatment groups (T2: 0.85–1.03; GdE: 0.06–0.12). There were 2143 patients (85.9%) with TEAEs (which were 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. As of May 2021, 190/2181 (8.7%) patients reported confirmed (n=160) or suspected (n=30) COVID-19. There were 3 COVID-19‒related deaths. Most COVID-19 cases (n=176/190 [92.6%]) were non-serious. Ozanimod was continued without interruption in 119 patients (62.6%) with COVID-19, of whom 113 recovered without sequelae; no patients with COVID-19 permanently discontinued ozanimod.

Conclusions: Interim data from patients in DAYBREAK treated for up to 62.7 months are consistent with the established safety profile of ozanimod and show sustained control of disease activity. The benefit:risk profile of ozanimod remains unchanged with most COVID-19 cases being non-serious, and the majority resolving without treatment interruption.

DMT14 Long-Term Efficacy and Safety, Including COVID-19 Outcomes, Among Ozanimod-Treated Patients with Relapsing Multiple Sclerosis in the Daybreak Open-Label Extension Trial

DMT14
Long-Term Efficacy and Safety, Including COVID-19 Outcomes, Among Ozanimod-Treated Patients with Relapsing Multiple Sclerosis in the Daybreak Open-Label Extension Trial