*From the first patient randomized (October 18, 2012)
through the DAYBREAK data cutoff (February 1, 2022), the maximum continuous exposure was 110.8 months. The mean
exposure to ZEPOSIA 0.92 mg in the parent trials and DAYBREAK was 70.4 months.4
aStudy designs: SUNBEAM
(1 year; N=1346) and RADIANCE (2 years; N=1313) were multicenter,
randomized, double-blind, double-dummy, active treatment-controlled studies of daily oral ozanimod 0.46 mg (not
approved for maintenance dose) or 0.92 mg vs weekly Avonex (interferon beta-1a), 30-μg intramuscular injection.
Primary endpoint: ZEPOSIA reduced ARR vs Avonex by 48% at 1 year (0.181 vs 0.350, respectively) and by 38% at 2
years (0.172 vs 0.276, respectively). Secondary endpoints: ZEPOSIA reduced the number of new or enlarging T2
lesions by 48% at 1 year and by 42% at 2 years and reduced the number of GdE lesions vs Avonex by 63% at 1 year
and 53% at 2 years. 9 of 10 patients showed no confirmed 3-month disability progression. There was no
significant difference in 3-month confirmed disability between ZEPOSIA and Avonex.1-3
bAdverse reactions: Overall
incidence of adverse reactions for ZEPOSIA vs Avonex at 1 year was 59.8% and 75.5%, respectively, and at 2 years
was 74.7% and 83.0%, respectively. Across 2 head-to-head trials, the most common adverse reactions with an
incidence of at least 2% in patients treated with ZEPOSIA and at least 1% greater than Avonex, respectively,
were as follows: upper respiratory infection, 26% (vs 23%); hepatic transaminase elevation, 10% (vs 5%);
orthostatic hypotension, 4% (vs 3%); urinary tract infection, 4% (vs 3%); back pain, 4% (vs 3%); hypertension,
4% (vs 2%); and abdominal pain upper, 2% (vs 1%). Data are not an adequate basis for comparison of rates between
ZEPOSIA and the active control. Severe adverse reactions: The rate of severe adverse reactions at 1 year
for ZEPOSIA was 1.6% vs 2.2% for Avonex and the rate at 2 years for ZEPOSIA was 3.5% vs 4.3% for Avonex.
Serious adverse reactions: The rate of serious adverse reactions at 1 year for ZEPOSIA was 2.9% vs 2.5%
for Avonex and the rate at 2 years for ZEPOSIA was 6.5% vs 6.4% for Avonex.2,3 Please see the full
Prescribing Information for additional SUNBEAM and RADIANCE data. See the IN PIVOTAL TRIALS table inside for
definitions of these terms.
cStudy design: DAYBREAK is an
ongoing open-label extension (OLE) trial that enrolled participants from multiple randomized phase 1 to 3
studies, including SUNBEAM and RADIANCE. These data are presented as an interim analysis with a data cutoff of
February 1, 2022. Patients evaluated in this analysis included those receiving the FDA-approved maintenance dose
of ZEPOSIA 0.92 mg (n=881) who completed the randomized phase 1 to 3 trials (the “continuous” arm), and those
who received ZEPOSIA 0.46 mg (n=877) or Avonex 30 μg (n=736) during phase 1 to 3 trials before receiving ZEPOSIA
0.92 mg at DAYBREAK baseline. The primary objective was to evaluate the long-term safety of ZEPOSIA. Secondary
efficacy outcomes included ARR, new/enlarging T2 lesions, and GdE lesions. Endpoints were analyzed
descriptively.1,4,5
Treatment-emergent adverse events (TEAEs): At the data
cutoff (up to 5 years), the overall incidence of TEAEs for ZEPOSIA in the DAYBREAK OLE trial was 84.7%. The most
common TEAEs with an incidence of at least 4% in patients treated with ZEPOSIA, sorted by decreasing incidence,
were as follows: nasopharyngitis, 19.3%; headache, 15.6%; upper respiratory tract infection, 10.9%; ALC
decreased, 8.9%; lymphopenia, 8.7%; back pain, 8.1%; GGT increased, 5.9%; bronchitis, 5.8%; urinary tract
infection, 5.8%; hypertension, 5.4%; respiratory tract infection, 5.4%; viral respiratory tract infection, 5.0%;
and depression-related TEAEs, 4.9%. The rate of TEAEs leading to permanent treatment discontinuation was 2.7%.
Severe TEAEs: The rate of severe TEAEs was 6.0%. Serious TEAEs: The rate of serious
TEAEs was 11.7%.4
RMS=relapsing forms of multiple sclerosis; ARR=annualized relapse rate; GdE=gadolinium enhancing;
SDMT=Symbol Digit Modalities Test.