Up to 9 Yearsb of Continuous Exposure in Multiple Sclerosis From Phase 1 Through DAYBREAK Data Cutoff1
multiple sclerosis (MS) and ulcerative colitis (UC)1,2c
in clinical trials (Phase 1-3 MS, Phase 2-3 UC) and post-marketing setting3,4
total exposure in clinical trials (Phase 1-3 MS, Phase 2-3 UC)
and post-marketing setting3,4
Overall ozanimod exposure in parent and extension trials (all indications) was 17,321.31 patient years (PY) and estimated to be 22,652 PY in the post-marketing setting. The cumulative number of patients exposed to ozanimod in parent and extension trials (all indications) was 3789 and estimated to be 34,910 in the post-marketing setting. All trials have a data cutoff of May 19, 2023 and all post-marketing data have a cutoff date of April 30, 2023.1,3,4
ZEPOSIA has been studied across multiple indications in 4 clinical trials, including TRUE NORTH (Ph 3); TOUCHSTONE (Ph 2); and SUNBEAM (Ph 3) and RADIANCE (Ph 3). 496 patients receiving the 0.92-mg dose of ZEPOSIA during induction in TRUE NORTH or TOUCHSTONE and 882 patients receiving the 0.92-mg dose of ZEPOSIA in SUNBEAM or RADIANCE were assessed in the safety analysis.
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.1
ZEPOSIA has been studied across multiple indications in 5 phase 3 clinical trials, including TRUE NORTH (NCT02435992), a multicenter, randomized, double-blind, placebo-controlled clinical trial; TRUE NORTH OLE (NCT02531126), a phase 3, multicenter, open-label extension trial for moderate to severe ulcerative colitis; SUNBEAM (NCT02294058); RADIANCE (NCT02047734); and DAYBREAK (NCT02576717).1
SUNBEAM (1 YEAR) | RADIANCE (2 YEARS) | ||||||
Summary of Adverse Reactions | Avonex n=445 | ZEPOSIA n=448 | Avonex n=440 | ZEPOSIA n=434 | |||
Overall incidence of adverse reactions | 75.5% | 59.8% | 83.0% | 74.7% | |||
Severe adverse reactions | 2.2% | 1.6% | 4.3% | 3.5% | |||
Serious adverse reactions | 2.5% | 2.9% | 6.4% | 6.5% |
SUNBEAM (1 YEAR) | |||
Summary of Adverse Reactions | Avonex n=445 | ZEPOSIA n=448 | |
Overall incidence of adverse reactions | 75.5% | 59.8% | |
Severe adverse reactions | 2.2% | 1.6% | |
Serious adverse reactions | 2.5% | 2.9% |
RADIANCE (2 YEARS) | |||
Summary of Adverse Reactions | Avonex n=440 | ZEPOSIA n=434 | |
Overall incidence of adverse reactions | 83.0% | 74.7% | |
Severe adverse reactions | 4.3% | 3.5% | |
Serious adverse reactions | 6.4% | 6.5% |
SUNBEAM AND RADIANCE: POOLED DATA
Adverse Reactions | Avonex n=885 | ZEPOSIA n=882 | |
Upper respiratory infectionb | 23% | 26% | |
Hepatic transaminase elevationc | 5% | 10% | |
Orthostatic hypotension | 3% | 4% | |
Urinary tract infection | 3% | 4% | |
Back pain | 3% | 4% | |
Hypertensiond | 2% | 4% | |
Abdominal pain upper | 1% | 2% |
Adverse reactions are sorted by decreasing incidence in patients treated with ZEPOSIA. For adverse reactions pertaining to liver function tests, increases were transient and generally resolved without discontinuation.2
Elevations of 3-fold the ULN or greater occurred in 5.5% of patients taking ZEPOSIA and in 3.1% of patients taking Avonex. The majority (79%) continued treatment with ZEPOSIA with values returning to less than 3 times the ULN within approximately 2 to 4 weeks.2
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.1
Data are not an adequate basis for comparison of rates between ZEPOSIA and the active control.2
Includes the following terms: nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, rhinitis, respiratory tract infection viral, viral upper respiratory tract infection, rhinorrhea, tracheitis, and laryngitis.2
Includes the following terms: alanine aminotransferase increased, gamma-glutamyl transferase (GG) increased, aspartate aminotransferase increased, hepatic enzyme increased, liver function test abnormal, and transaminases increased.2
Includes hypertension, essential hypertension, and orthostatic hypertension.2
DAYBREAK OLE: Incidence of Adverse Events1
Summary Of TEAEs (PRIMARY ENDPOINT) | ZEPOSIA (n=2494) | IR/1000 PY | |
Any TEAE | 88.2% | 657.0 | |
Severe TEAEs | 8.9% | 19.6 | |
Serious TEAEs | 14.1% | 32.0 | |
TEAEs leading to permanent treatment discontinuation | 3.6% | 7.6 |
TEAEs | ZEPOSIA (N=2494) | IR/1000 PY | |
Nasopharyngitis | 20.6% | 51.0 | |
Headache | 16.9% | 40.3 | |
Upper respiratory tract infection | 11.9% | 27.3 | |
Lymphopeniae | 10.5% | 24.2 | |
ALC decreasede | 9.2% | 20.9 | |
Back pain | 9.1% | 20.5 | |
Hypertensionf | 8.7% | 19.5 | |
GGT increased | 7.3% | 16.3 | |
Arthralgia | 6.3% | 13.8 | |
Respiratory tract infection | 6.3% | 13.8 | |
Urinary tract infection | 6.3% | 13.8 | |
Bronchitis | 6.2% | 13.6 | |
Viral respiratory tract infection | 5.5% | 12.0 | |
Depression-related TEAEsg | 5.5% | 12.0 |
Similar safety patterns were seen in the continuous ZEPOSIA 0.92 mg (n=881) population1
ALC reductions are an expected pharmacodynamic effect related to the mechanism of ozanimod; although investigators were not required to report ALC reductions as TEAEs, lymphopenia and ALC decreases were reported as TEAEs according to investigator determination.1
Includes preferred terms of hypertension, essential hypertension, labile hypertension, and systolic hypertension.1
Includes preferred terms of depression, depressed mood, and depressive symptoms.1
Demonstrated Tolerability Profile With Low Discontinuation Rates Due to Adverse Events1,2,5,6
SUNBEAM (1 Year)
Remained on ZEPOSIA at 1 Year and 92% remained on Avonex2
RADIANCE (2 Years)
Remained on ZEPOSIA at 2 Years and 85% remained on Avonex2
SUNBEAM (1 Year)
For ZEPOSIA and 3.6% for Avonex5
RADIANCE (2 Years)
For ZEPOSIA and 4.1% for Avonex6
DAYBREAK (Up to 6 Years) n=2494
For ZEPOSIA in Long-Term Extension Study1
Rates of Serious Infections
and Malignancies Consistent
vs Avonex
The rate of serious infections at 1 year for ZEPOSIA was 1.1% vs 0.7% for Avonex, and the rate at 2 years for ZEPOSIA
was 0.9% vs 0.9% for Avonex. The rate of malignancies at 1 year for ZEPOSIA was 0.2% vs 0% for Avonex, and the rate at 2 years for ZEPOSIA was 0.9% vs 0.5% for Avonex.5,6
► Overall Infections
In SUNBEAM and RADIANCE, the overall rate of infections with ZEPOSIA (35%) was similar to Avonex (34%). ZEPOSIA causes a reduction in peripheral blood lymphocyte count and may increase the risk of infection.2
Controlled Lymphocyte Reductions
ALC was consistently maintained near the lower limit of normal across both pivotal trials, and the mean ALC for both SUNBEAM and RADIANCE was ≈0.8 × 109/L.5-7
VIEW ALC DATAHerpetic Infections: In active-controlled MS trials, herpes zoster was reported as an adverse reaction in 0.6% of patients treated with ZEPOSIA 0.92 mg and in 0.2% of patients taking Avonex.2
ZEPOSIA Consistently Maintained ALC Near the Lower Limit of Normal5,6
Lymphocyte numbers can be restored to normal values by discontinuing therapy2,6,8
BL=baseline; LLN=lower limit of normal.
Herpetic Infections: In active-controlled MS trials, herpes zoster was reported as an adverse reaction in 0.6% of patients treated with ZEPOSIA 0.92 mg and in 0.2% of patients taking Avonex.2
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