Safety Patterns over Time with Ozanimod During an Open-label Extension Trial in Patients with Relapsing Multiple Sclerosis
Krzysztof Selmaj1, Tjalf Ziemssen2, Giancarlo Comi3, Hans-Peter Hartung4, Jennifer Reardon5, Andrew Thorpe5, Jon Riolo5, Chun-Yen Cheng5, James Sheffield5, Anthony Krakovich5, Patrick Vermersch6, Bruce Cree7
1Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 2Department of Neurology, Center of Clinical Neuroscience, Carl Gustav Carus University Clinic, University Hospital of Dresden, Dresden, Germany, 3Vita-Salute San Raffaele University and Casa di Cura Igea, Milan, Italy, 4Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Medical University of Vienna, Vienna, Austria; and Palacky University Olomouc, Olomouc, Czech Republic, 5Bristol Myers Squibb, Princeton, New Jersey, 6Univ. Lille, Inserm UMR 1172, CHU Lille, FHU Precise, Lille, France, 7Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California
Objective:
To describe patterns of treatment-emergent adverse events (TEAEs) over time in ozanimod-treated patients with relapsing multiple sclerosis (RMS).
Background:
Ozanimod is a sphingosine 1-phosphate receptor 1 and 5 modulator approved in multiple countries for the treatment of adults with relapsing forms of multiple sclerosis (RMS) or moderately to severely active ulcerative colitis.
Design/Methods:
In two phase 3 trials, adults with RMS were randomized to ozanimod 0.46mg/d or 0.92mg/d or interferon β-1a 30µg/wk for ≥12 months (SUNBEAM‒NCT02294058) or 24 months (RADIANCE‒NCT02047734). Patients who completed RMS ozanimod trials could enroll in an open-label extension (OLE) trial of ozanimod 0.92mg/d (DAYBREAK‒NCT02576717). Rates of TEAEs were calculated at yearly intervals during the OLE trial (database lock: April 7, 2023).
Results:
The proportion of patients treated with continuous ozanimod 0.92mg (n=762) who experienced TEAEs (n/N [%]) decreased over time (from OLE Month 12 to OLE >60–72 months) for overall TEAEs (437/762 [57.3] vs 190/619 [30.7]), serious TEAEs (24/762 [3.1] vs 12/619 [1.9]), infections (217/762 [28.5] vs 106/619 [17.1]), opportunistic infections (15/762 [2.0] vs 2/619 [0.3]), and hepatic disorder TEAEs (32/762 [4.2] vs 7/619 [1.1]), and remained relatively stable for serious infections (5/762 [0.7] vs 5/619 [0.8]), cardiac disorder TEAEs (3/762 [0.4] vs 4/619 [0.6]), and malignancies (2/762 [0.3] vs 2/619 [0.3]). Oral herpes and herpes zoster were the most common opportunistic infections at OLE Month 12; rates decreased over time. From OLE baseline to Month 12, no single serious infection occurred in >1 patient; the most common serious infection at >60–72 months was COVID-19 (3/619 [0.5]).
Conclusions:
The proportion of patients with RMS who experienced TEAEs in the OLE trial decreased over 6 years of ozanimod 0.92 mg treatment.