Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1−3 trials

Abstract

Background:
Ozanimod, an oral sphingosine 1-phosphate receptor 1 and 5 modulator, is approved in the US and EU for treatment of relapsing multiple sclerosis (RMS).

Methods:
RMS participants who completed a phase 1–3 ozanimod trial were eligible for DAYBREAK (NCT02576717), an ongoing open-label extension (OLE) trial of ozanimod 0.92 mg/d (equivalent to ozanimod HCl 1 mg). The primary objective was to evaluate safety. Efficacy was evaluated with annualized relapse rate (ARR), calculated via European Charcot Foundation 2020 3001 Safety and Efficacy Page 2 of 2 negative binomial regression and pooled for all parent-trial treatment groups.
Number of new/enlarging T2 and gadolinium-enhancing (GdE) MRI brain lesions were reported for those who entered the OLE from a phase 3 parent trial.

Results:
This interim analysis (data cut 20 December 2019; presented at ACTRIMS-ECTRIMS 2020) included 2494 participants with mean (range) ozanimod exposure of 35.4 (0.03–50.2) months in the OLE. Adjusted ARR in the OLE was 0.112 (95% CI, 0.093‒0.135). At months 24 and 36, 79% and 75% of participants, respectively, were relapse free in the OLE. Three- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of OLE participants, respectively. At 24 months, mean number of new/enlarging T2 lesions per scan was similar across parent-trial treatment groups (range, 1.57–1.90), as was mean number of GdE lesions (0.2‒0.4). In the OLE, 2039 participants (81.8%) had treatment-emergent adverse events (TEAEs), and 236 (9.5%) had serious TEAEs (SAEs). These rates were similar across parent-trial treatment groups. The most common TEAEs were nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%). There were no serious opportunistic infections. Exposure-adjusted TEAE and SAE incidence rates have decreased over time.

Conclusions:
Ozanimod was associated with low ARR and new/enlarging T2 and GdE lesion counts. Most participants were relapse free and did not experience disability progression. No new safety concerns emerged with long-term use.

Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1−3 trials

Krzysztof W. Selmaj,1 Lawrence Steinman,2 Giancarlo Comi,3 Amit Bar-Or,4 Douglas L. Arnold,5 Hans-Peter Hartung,6 Xavier Montalban,7 Eva K. Havrdová,8 James K. Sheffield,9 Hongjuan Liu,9 Neil Minton,9 Diego Silva,9 Ludwig Kappos,10 Jeffrey A. Cohen,11 Bruce A. C. Cree12

1Center for Neurology, Łódz, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland; 2Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, USA; 3Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; 4Center for Neuroinflammation and Experimental Therapeutics, and Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 5NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada; 6Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; 7Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitario Vall d'Hebron, Barcelona, Spain; 8Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty, Charles University, Prague, Czech Republic; 9Bristol-Myers Squibb Company, Princeton, New Jersey, USA; 10Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland; 11Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA; 12Weill Institute for Neurosciences, Department of Neurology, UCSF University of California San Francisco, San Francisco, California, USA