Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program

Krzysztof W Selmaj; Jeffrey A Cohen; Giancarlo Comi; Amit Bar-Or; Douglas L Arnold; Lawrence Steinman; Hans Peter Hartung; Xavier Montalban; Eva Kubala Havrdova; Bruce A C Cree; Neil Minton; James K Sheffield; Ning Ding; Ludwig Kappos

doi:10.1016/j.msard.2021.102844

Ozanimod in relapsing multiple sclerosis: Pooled safety results from the clinical development program

Mult Scler Relat Disord. 2021 Jun:51:102844. doi: 10.1016/j.msard.2021.102844. Epub 2021 Feb 15.

Authors

Affiliations

¹ Center for Neurology, Tylna 12, 90-324 Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Warszawska 30, 11-082 Olsztyn, Poland. Electronic address: [email protected].
² Department of Neurology, Mellen Center for MS Treatment and Research, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio, 44195, USA. Electronic address: [email protected].
³ Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, via Olgettina 48, 20132 Milan, Italy. Electronic address: [email protected].
⁴ Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street - 3 Dulles Building, Philadelphia, Pennsylvania, 19104, USA. Electronic address: [email protected].
⁵ NeuroRx Research and Montréal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec, H3A 2B4,Canada. Electronic address: [email protected].
⁶ Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, 300 Pasteur Dr Stanford, Stanford, California 94305, USA. Electronic address: [email protected].
⁷ Department of Neurology, Medical Faculty, Heinrich-Heine University, University Hospital Dusseldorf, Moorenstr. 5 40225 Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Camperdown, NSW 2006 Sydney, Australia; Department of Neurology, Medical University Vienna, Spitalgasse 23, 1090 Vienna, Austria. Electronic address: [email protected].
⁸ Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Pg. Vall d'Hebron, 119-129, 08035 Barcelona, Spain. Electronic address: [email protected].
⁹ Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Katerinska 30, 120 00 Prague 2 Czech Republic. Electronic address: [email protected].
¹⁰ Weill Institute for Neurosciences, Department of Neurology, UCSF University of California San Francisco, 675 Nelson Rising Lane San Francisco, California 94158, USA. Electronic address: [email protected].
¹¹ Bristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, New Jersey 08648, USA. Electronic address: [email protected].
¹² Bristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, New Jersey 08648, USA. Electronic address: [email protected].
¹³ Bristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, New Jersey 08648, USA. Electronic address: [email protected].
¹⁴ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Medicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Electronic address: [email protected].

PMID: 33892317
DOI: 10.1016/j.msard.2021.102844

Abstract

Background: Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in multiple countries for the treatment of relapsing multiple sclerosis (RMS). In phase 3 trials, ozanimod was well tolerated and superior to interferon beta-1a 30 µg once-weekly in reducing clinical and radiologic disease activity. The objective of this integrated safety analysis was to evaluate the safety of extended ozanimod exposure in participants with RMS from all clinical trials and compare it with phase 3 trial data.

Methods: We report pooled incidence and study duration‒adjusted incidence rates (IR) of treatment-emergent adverse events (TEAEs) from an interim data cut (January 31, 2019) of RMS participants treated with ozanimod. Data were pooled from a phase 1 pharmacokinetic/pharmacodynamic trial, a placebo-controlled phase 2 trial with dose-blinded extension, 2 large active-controlled phase 3 trials, and an open-label extension (OLE). Results were compared with pooled phase 3 trial data.

Results: At the data cutoff, 2631 RMS participants had exposure to ozanimod 0.92 mg (mean 32.0 months) and 2787 had exposure to either ozanimod 0.46 or 0.92 mg (mean 37.1 months). The IRs per 1000 person-years (PY) for any TEAE (772.2) and serious TEAEs (33.2) in the overall population were similar to those in the phase 3 population (896.1 and 31.2, respectively). There were no serious opportunistic infections. There were no second-degree or higher atrioventricular blocks on electrocardiogram. Hepatic enzyme elevations declined over time. Malignancy rates remained low with longer exposure. Pulmonary function tests showed minimal reductions in lung function. Seven ozanimod-treated participants with comorbid risk factors had confirmed macular edema, including 3 in the ongoing OLE.

Conclusions: Safety results in this larger RMS population with greater ozanimod exposure demonstrated no new safety concerns and were consistent with phase 3 trial results.

Keywords: Adverse events; Clinical trials; Multiple sclerosis; Ozanimod; Safety.

MeSH terms

Humans
Indans
Multiple Sclerosis*
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / epidemiology
Oxadiazoles

Substances

Indans
Oxadiazoles
ozanimod