*From first patient randomized (October 18, 2012) through the DAYBREAK data cutoff (February 2, 2021), mean (range) continuous ozanimod 0.92 mg exposure was 67.4 (6.01-98.8) months.5
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. Upper respiratory infection includes nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, rhinitis, respiratory tract infection viral, viral upper respiratory tract infection, rhinorrhea, tracheitis, and laryngitis. Hepatic transaminase elevation includes alanine aminotransferase increased, gamma-glutamyl transferase increased, aspartate aminotransferase increased, hepatic enzyme increased, liver function test abnormal, and transaminase increased. Hypertension includes hypertension, essential hypertension, and orthostatic hypertension. 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
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. This data is presented as an interim analysis with a data cutoff of February 2, 2021. Patients evaluated in this analysis included those receiving ZEPOSIA 0.92 mg (n=881) who completed the randomized phase 1 to 3 trials. Primary objective evaluated the long-term safety of ZEPOSIA. Secondary objectives included ARR, new/enlarging T2 lesions, and GdE lesions. Endpoints were analyzed descriptively.4
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.