BACKGROUND: Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively 
binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 
study showed that ozanimod had better efficacy than placebo on MRI measures, 
with a favourable safety profile, in participants with relapsing multiple 
sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod 
versus intramuscular interferon beta-1a in participants with relapsing multiple 
sclerosis.
METHODS: SUNBEAM was a randomised, double-blind, double-dummy, active-controlled 
phase 3 trial done at 152 academic medical centres and clinical practices in 20 
countries. We enrolled participants aged 18-55 years with relapsing multiple 
sclerosis, baseline expanded disability status scale (EDSS) score of 0·0-5·0, 
and either at least one relapse within the 12 months before screening or at 
least one relapse within 24 months plus at least one gadolinium-enhancing lesion 
within 12 months before screening. Participants were randomly assigned 1:1:1 by 
a blocked algorithm stratified by country and baseline EDSS score to at least 12 
months treatment of either once-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 assignment. The primary endpoint was annualised 
relapse rate (ARR) during the treatment period and was assessed in the 
intention-to-treat population. Safety was assessed in all participants according 
to the highest dose of ozanimod received. This trial is registered at 
ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014-002320-27.
FINDINGS: Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were 
enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg 
(n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the 
study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; 
and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28-0·44) for 
interferon beta-1a, 0·18 (95% CI 0·14-0·24) for ozanimod 1·0 mg (rate ratio [RR] 
of 0·52 [0·41-0·66] vs interferon beta-1a; p<0·0001), and 0·24 (0·19-0·31) for 
ozanimod 0·5 mg (RR 0·69 [0·55-0·86] vs interferon beta-1a; p=0·0013). Few 
ozanimod-treated participants discontinued treatment because of adverse events 
(13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 
mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically 
significant bradycardia or second-degree or third-degree atrioventricular block 
was reported. The incidence of serious adverse events was low and similar across 
treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] 
who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No 
serious opportunistic infections occurred in ozanimod-treated participants.
INTERPRETATION: In participants with relapsing multiple sclerosis treated for at 
least 12 months, ozanimod was well tolerated and demonstrated a significantly 
lower relapse rate than interferon beta-1a. These findings provide support for 
ozanimod as an oral therapy for individuals with relapsing multiple sclerosis.
FUNDING: Celgene International II.