Efficacy and Safety of Ozanimod Versus Interferon Beta 1A

Friday, June 1, 2018: 3:25 PM
209 (Nashville Music City Center)
Bruce AC Cree, MD, PhD , UCSF Neurology, Weill Institute for Neurosciences, San Francisco, CA
Amit Bar-Or, MD , Center for Neuroinflammation and Therapeutics, and Multiple Sclerosis Division, University of Pennsylvania, Philadelphia, PA
Giancarlo Comi, MD , Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
Krzysztof W Selmaj, MD, PhD , Medical University of Lodz, Lodz, Poland
Douglas L Arnold, MD , Montreal Neurological Institute, McGill University, Montreal, QC, Canada
Lawrence Steinman, MD , Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA
Hans-Peter Hartung, MD , Department of Neurology, Medical Faculty, Heinrich-Heine University, Dusseldorf, Germany
Xavier Montalban, MD , Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall díHebron, 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 , Receptos, a wholly owned subsidiary of Celgene, San Diego, CA
Kartik Raghupathi, PhD , Receptos, a wholly owned subsidiary of Celgene, San Diego, CA
Ludwig Kappos, MD , University Hospital Basel, University of Basel, Basel, Switzerland
Jeffrey A Cohen, MD , Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH

Background: Ozanimod, an oral, once-daily immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.

Objectives: Compare efficacy and safety of ozanimod vs interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) patients from SUNBEAM (NCT02294058) and RADIANCE Part B (NCT02047734).

Methods: Patients received ozanimod HCl 1 or 0.5 mg (with a 7-day dose escalation) vs IFN β-1a 30 µg. We report efficacy from SUNBEAM (12 months) and RADIANCE (24 months), and pooled safety.

Results: 1346 and 1313 patients were treated in SUNBEAM and RADIANCE, respectively. Ozanimod 1 and 0.5 mg reduced adjusted annualized relapse rate (ARR) by 48% (0.181; P<0.0001) and 31% (0.241; P=0.0013) vs IFN (0.350) in SUNBEAM, respectively, and by 38% (0.172; P<0.0001) and 21% (0.218; P=0.0167) vs IFN (0.276) in RADIANCE, respectively.

Adjusted mean number of new/enlarging T2 lesions was reduced by 48% (P<0.0001) and 25% (P=0.0032) vs IFN for ozanimod 1 and 0.5 mg, respectively, over 12 months in SUNBEAM, and reduced by 42% (P<0.0001) and 34% (P=0.0001), respectively, vs IFN over 24 months in RADIANCE.

Adjusted mean number of gadolinium enhancing lesions was reduced for ozanimod vs IFN (SUNBEAM: ozanimod 1 mg, 63% lower [P<0.0001]; 0.5 mg, 34% lower [P=0.0182]; RADIANCE: ozanimod 1 mg, 53% lower [P=0.0006]; 0.5 mg, 47% lower [P=0.0030]). Confirmed 3-month pooled disability progression was low across the ozanimod 1 mg (0.102), 0.5 mg (0.080), and IFN (0.099) groups. Whole brain volume loss (BVL) was lower with ozanimod vs IFN (SUNBEAM: ozanimod 1 mg, 33% lower; 0.5 mg, 12% lower; RADIANCE: ozanimod 1 mg, 27% lower; 0.5 mg, 25% lower), with greater slowing of cortical gray matter and thalamic volume loss in both studies.

Compared with IFN, ozanimod-treated patients had fewer adverse events (AEs) (ozanimod 1 mg, 67.1%; 0.5 mg, 65.6%; IFN, 79.2%) and AEs leading to study drug discontinuation (ozanimod 1 mg, 2.9%; 0.5 mg, 2.4%; IFN, 3.8%). Serious AEs, including infections, were balanced and infrequent across groups (ozanimod 1 mg, 4.6%; 0.5 mg, 5.3%; IFN, 4.4%); no serious opportunistic infections were reported. No second degree or higher atrioventricular block was observed. There was one death due to drowning (ozanimod 0.5 mg), unrelated to study drug.

Conclusions: Both ozanimod 1 mg and 0.5 mg demonstrated superiority to IFN on ARR and MRI endpoints. These findings, coupled with safety/tolerability results, suggest that oral ozanimod has a favorable benefit-risk profile in RMS.