BACKGROUND: Ozanimod is a sphingosine 1-phosphate receptor modulator, which 
selectively binds to sphingosine 1-phosphate receptor subtypes 1 and 5 with high 
affinity. In the RADIANCE phase 2 study in participants with relapsing multiple 
sclerosis, ozanimod was associated with better efficacy than placebo on MRI 
measures and was well tolerated. The RADIANCE phase 3 study aimed to confirm the 
safety and efficacy of ozanimod versus interferon beta-1a in individuals with 
relapsing multiple sclerosis.
METHODS: We did a 24-month, multicentre, double-blind, double-dummy phase 3 
trial in participants with relapsing multiple sclerosis at 147 medical centres 
and clinical practices in 21 countries. Participants were aged 18-55 years, had 
multiple sclerosis according to 2010 McDonald criteria, a relapsing clinical 
course, brain MRI lesions consistent with multiple sclerosis, an expanded 
disability status scale score of 0·0-5·0, and either at least one relapse within 
12 months before screening or at least one relapse within 24 months before 
screening plus at least one gadolinium-enhancing lesion within the 12 months 
before randomisation. Participants were randomly assigned (1:1:1) via an 
interactive voice response system to daily oral ozanimod 1·0 mg or 0·5 mg or 
weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and 
study staff were masked to treatment allocation. The primary endpoint was 
annualised relapse rate (ARR) over 24 months. The primary analysis was done in 
the intention-to-treat population of all participants who received study drug 
and safety was assessed in all randomly assigned participants who received study 
drug, grouped by highest dose of ozanimod received. This trial is registered at 
ClinicalTrials.gov, NCT02047734, and EudraCT, 2012-002714-40.
FINDINGS: Between Dec 27, 2013, and March 31, 2015, we screened 1695 
participants, of which 375 did not meet inclusion criteria. 1320 participants 
were enrolled and randomly assigned to a group, of whom 1313 received study drug 
(433 assigned to ozanimod 1·0 mg, 439 assigned to ozanimod 0·5 mg, and 441 
assigned to interferon beta-1a) and 1138 (86·7%) completed 24 months of 
treatment. Adjusted ARRs were 0·17 (95% CI 0·14-0·21) with ozanimod 1·0 mg, 0·22 
(0·18-0·26) with ozanimod 0·5 mg, and 0·28 (0·23-0·32) with interferon beta-1a, 
with rate ratios versus interferon beta-1a of 0·62 (95% CI 0·51-0·77; p<0·0001) 
for ozanimod 1·0 mg and 0·79 (0·65 to 0·96; p=0·0167) for ozanimod 0·5 mg. The 
incidence of treatment-emergent adverse events was higher in the interferon 
beta-1a group (365 [83·0%] of 440 participants) than in the ozanimod 1·0 mg 
group (324 [74·7%] of 434) or the ozanimod 0·5 mg group (326 [74·3%] of 439). 
More participants in the interferon beta-1a group had treatment-emergent adverse 
events leading to treatment discontinuation than in the ozanimod groups. 
Incidences of infections and serious treatment-emergent adverse events were 
similar across treatment groups. No cases of ozanimod-related symptomatic 
reduction in heart rate and no second-degree or third-degree cases of 
atrioventricular block were reported.
INTERPRETATION: In this 24-month phase 3 study in participants with relapsing 
multiple sclerosis, ozanimod was well tolerated and associated with a 
significantly lower rate of clinical relapses than intramuscular interferon 
beta-1a. These findings show the potential of ozanimod as an effective oral 
therapy for individuals with relapsing multiple sclerosis.
FUNDING: Celgene International II.