SUNBEAM

Ozanimod

SUNBEAM showed that once-daily ozanimod reduced relapses more than weekly intramuscular interferon beta-1a.

Phase
Phase III
Population
Relapsing multiple sclerosis (RMS)
Controlled period
Dec 3, 2014 — Dec 22, 2016

What was compared

RandomizedDouble-blindDouble-dummyActive-controlled
Intervention

Ozanimod 1.0 mg

Orally once daily

n=447
Comparator

Interferon beta-1a

30 μg intramuscularly once weekly

n=448

Additional randomized arm

Ozanimod 0.5 mg

Orally once dailyn=451
1,346 randomizedMinimum 12 months controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

Treatment period, minimum 12 months

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

Treatment period, minimum 12 months
Ozanimod 1.0 mg
0.18
Ozanimod 0.5 mg
0.24
Interferon beta-1a
0.35

Rate ratios 0.52 (P<0.0001) and 0.69 (P=0.0013) versus interferon.

Selected secondary outcomes

Treatment discontinuation

2.9%, 1.5%, and 3.6% discontinued for adverse events, respectively.

MRI

Key inflammatory MRI outcomes favored ozanimod.

Who was studied

Key inclusion criteria

  • Age 18–55 years
  • RMS diagnosis based on McDonald criteria 2010
  • Baseline EDSS 0–5.0; MRI lesions consistent with MS
  • At least 1 relapse in the previous year, or at least 1 in the previous 2 years plus a gadolinium-enhancing lesion in the previous year
  • No relapse, systemic corticosteroids, or ACTH from 30 days before screening through randomization
  • Varicella-zoster immunity or vaccination at least 30 days before randomization

Key exclusion criteria

  • PPMS
  • MS duration > 15 years with EDSS ≤ 2.0
  • Contraindication to MRI or gadolinium
  • Previous interferon intolerance
  • Resting heart rate < 55 beats/min or specified cardiac conditions
  • Previous lymphocyte-depleting or lymphocyte-trafficking-blocking therapy
  • Active infection

Participants at baseline

CharacteristicOzanimod 1 mgN=447Ozanimod 0.5 mgN=451IFNβ-1aN=448
Age, years — mean ± SD34.8 ± 9.236.0 ± 9.435.9 ± 9.1
Female sex — n (%)283 (63.3%)311 (69.0%)300 (67.0%)
Time since MS symptom onset, years — mean ± SD6.9 ± 6.47.2 ± 6.36.9 ± 5.9
Time since MS diagnosis, years — mean ± SD3.6 ± 4.23.7 ± 4.53.7 ± 4.4
EDSS — mean ± SD2.6 ± 1.22.7 ± 1.12.6 ± 1.1
Relapses in previous 12 months — mean ± SD1.3 ± 0.61.3 ± 0.61.3 ± 0.6
Previous DMT — n (%)128 (28.6%)132 (29.3%)151 (33.7%)

SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy; IFNβ: interferon beta.

Source: Comi et al., Lancet Neurology 2019, Table 1

Safety signal

  • Serious adverse-event incidence was low and similar across groups.
  • No clinically significant first-dose bradycardia, high-grade atrioventricular block, or serious opportunistic infection was reported in ozanimod-treated participants.

Why it mattered

SUNBEAM showed that an oral, more receptor-selective S1P modulator reduced relapses and MRI activity compared with weekly intramuscular interferon beta-1a. It broadened the S1P treatment program, while its short follow-up and nonsignificant disability result kept the conclusion centered on inflammatory activity.

Important limitation

Follow-up varied with a minimum of 12 months, limiting disability and uncommon-safety conclusions compared with longer fixed-duration trials.

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