Up to 9 Years* of Patient Exposure From Phase 1 Trials Through Ongoing Open-Label Extension Study1-5

The Largest Number of Patients With RMS Studied in Pivotal
Head-to-Head Trials With an Active Comparator (N=2659)2,3a
SUNBEAM and RADIANCE study designs SUNBEAM and RADIANCE study designs
PHASE 3 ENDPOINTS1
PRIMARY
  • Annualized Relapse Rate
KEY SECONDARY
  • GdE Lesions
  • New/Enlarging T2 Lesions
  • Confirmed Disability Progression
*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
a2659 patients includes all 3 arms of the study: the 0.92-mg dose of ZEPOSIA, the 0.46-mg dose of ZEPOSIA, and the 30-μg dose of Avonex.2,3
Chart outlining DAYBREAK study structure Chart outlining DAYBREAK study structure
DAYBREAK ENDPOINTS6
PRIMARY
  • Long-Term Safety
KEY SECONDARY
  • Annualized Relapse Rate
  • GdE Lesions
  • New/Enlarging T2 Lesions
bDAYBREAK is an ongoing open-label extension (OLE) trial that enrolled participants from multiple randomized phase 1 to 3 studies, including SUNBEAM and RADIANCE, and is presented as an interim analysis with a data cutoff of February 1, 2022. Endpoints were analyzed descriptively. The overall population (n=2494) in DAYBREAK consists of the continuous 0.92 mg population (n=881) and additional participants who received any study treatment other than ZEPOSIA 0.92 mg during the parent studies, including 10 participants from phase 1 (ZEPOSIA 0.46 mg, n=10), 109 participants from phase 2 (ZEPOSIA 0.46 mg, n=109), 805 participants from phase 3 SUNBEAM (Avonex 30 μg, n=392; ZEPOSIA 0.46 mg, n=413), and 689 participants from phase 3 RADIANCE (Avonex 30 μg, n=344; ZEPOSIA 0.46 mg, n=345).4,5
cAt data cutoff, mean (range) continuous ozanimod 0.92 mg exposure in DAYBREAK was 56.4 (0.03-74.7) months.4
dThe overall population contains all patients who received at least 1 dose of ZEPOSIA 0.92 mg during DAYBREAK OLE. The continuous population includes patients who received ZEPOSIA 0.92 mg in randomized phase 1-3 studies and continued on ZEPOSIA in DAYBREAK. The recommended dose for ZEPOSIA is 0.92 mg.1,4
RMS=relapsing multiple sclerosis.
Key Inclusion Criteria1-3
  • Ages 18 to 55
  • EDSS score of 0.0 to 5.0
  • Experienced ≥1 relapse within the previous year
    OR 1 relapse within prior 2 years with ≥1 GdE
    lesion in prior year
Key Exclusion Criteria1-3
  • Primary progressive MS
  • Specific cardiac conditions (eg, recent MI/stroke,
    prolonged QTcF interval)
  • Resting heart rate <55 bpm at screening
  • T1DM or uncontrolled T2DM with hemoglobin A1C >9%
    (SUNBEAM) OR >7% (RADIANCE), or patients with
    diabetes with significant comorbidities
Baseline Characteristics1d
Characteristics (Mean Or %) SUNBEAM RADIANCE
Age (years) 35.4 35.6
Race, white 99.8% 98%
Sex, female 65% 68%
Time since MS symptom onset (years) 6.9 6.6
EDSS score (median) 2.5 2.5
Previously treated with MS therapiese 31% 29%
Number of relapses in prior year 1.3 1.3
≥1 T1 GdE lesion 48% 43%
Number of T1 GdE lesions 1.8 1.7
dIncludes the 0.92-mg dose of ZEPOSIA and the 30-μg dose of Avonex. The 0.46-mg dose of ZEPOSIA is not included.1
eIncludes those previously treated with non-steroid therapy for MS.1
A1C=glycated hemoglobin; BPM=beats per minute; EDSS=Expanded Disability Status Scale; MI=myocardial infarction; MS=multiple sclerosis; QTcF=prolonged Fridericia-corrected QT; T1DM=type 1 diabetes mellitus; T2DM=type 2 diabetes mellitus.
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IMPORTANT SAFETY INFORMATION
Contraindications:
  • Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • Patients with severe untreated sleep apnea
  • Patients taking a monoamine oxidase (MAO) inhibitor
Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA.
  • Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.
  • Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
  • In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.
  • Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.
Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability.

PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.

If confirmed, treatment with ZEPOSIA should be discontinued.

Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:
  • with significant QT prolongation
  • with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
  • with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
  • with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block
Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease.
Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com.
Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA.
Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated.
Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued.
Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued.
Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended.
Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation.
Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA.
Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache.

Use in Specific Populations: Hepatic Impairment: Use is not recommended.
For additional safety information, please see the full Prescribing Information and Medication Guide
INDICATIONS
ZEPOSIA® (ozanimod) is indicated for the treatment of:
  1. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
  2. Moderately to severely active ulcerative colitis (UC) in adults.
References:
  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company; 2022.
  2. Comi G, Kappos L, Selmaj KW, et al; SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020 and Suppl 1-26. doi:10.1016/S1474-4422(19)30239-X.
  3. Cohen JA, Comi G, Selmaj KW, et al; RADIANCE Trial Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033 and Suppl 1-31. doi:10.1016/S1474-4422(19)30238-8.
  4. Selmaj KW et al. Poster presented at ECTRIMS; October 26-28, 2022; Amsterdam, Netherlands. Poster P334.
  5. Selmaj KW, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1-3 trials. Presented at: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11-13, 2020; MSVirtual2020. Presentation P0217.
References:
  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company; 2022.
  2. Comi G, Kappos L, Selmaj KW, et al; SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020 and Suppl 1-26. doi:10.1016/S1474-4422(19)30239-X.
  3. Cohen JA, Comi G, Selmaj KW, et al; RADIANCE Trial Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033 and Suppl 1-31. doi:10.1016/S1474-4422(19)30238-8.
  4. Selmaj KW et al. Poster at 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); October 13-15, 2021; The Digital Experience. P737.
  5. Cree BAC, Selmaj KW, Steinman L, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial. Mult Scler. 2022;28(12):1944-1962. doi:10.1177/13524585221102584.
  6. Selmaj KW, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1-3 trials. Presented at: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11-13, 2020; MSVirtual2020. Presentation P0217.
References:
  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb Company.
  2. Selmaj KW et al. Poster at 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); October 13-15, 2021; The Digital Experience. P737.
  3. Comi G, Kappos L, Selmaj KW, et al; SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020 and Suppl 1-26. doi:10.1016/S1474-4422(19)30239-X
  4. Cohen JA, Comi G, Selmaj KW, et al; RADIANCE Trial Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033 and Suppl 1-31. doi:10.1016/S1474-4422(19)30238-8
  5. Selmaj KW, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1-3 trials. Presented at: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11-13, 2020; MSVirtual2020. Presentation P0217.
  6. Cree BAC, Selmaj KW, Steinman L, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial. Mult Scler. 2022;28(12):1944-1962. doi:10.1177/13524585221102584
  7. DeLuca J, Schippling S, Montalban X, et al. Effect of ozanimod on Symbol Digit Modalities Test performance in relapsing MS. Mult Scler Relat Disord. 2021;48:102673. doi:10.1016/j.msard.2020.102673.
  8. Deluca J, Cohen JA, Cree BAC, et al. Effects of ozanimod on information processing speed: findings from the phase 3 SUNBEAM and DAYBREAK extension trials. Poster presented on: American Academy of Neurology (2020) Virtual Platform. Poster 1-017.
  9. Drake AS, Weinstock-Guttman B, Morrow SA, Hojnacki D, Munschauer FE, Benedict RHB. Psychometrics and normative data for the Multiple Sclerosis Functional Composite: replacing the PASAT with the Symbol Digit Modalities Test. Mult Scler. 2010;16(2):228-237. doi:10.1177/1352458509354552
  10. Benedict RHB, DeLuca J, Phillips G, et al. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler. 2017;23(5):721-733. doi:10.1177/1352458517690821
References:
  1. Selmaj KW et al. Poster presented at ECTRIMS; October 26-28, 2022; Amsterdam, Netherlands. Poster P334.
  2. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company; 2022.
  3. Data on file. BMS-REF-OZA-0028. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Data on file. BMS-REF-OZA-0029. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  5. Comi G, Kappos L, Selmaj KW, et al; SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020 and Suppl 1-26. doi:10.1016/S1474-4422(19)30239-X
  6. Cohen JA, Comi G, Selmaj KW, et al; RADIANCE Trial Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033 and Suppl 1-31. doi:10.1016/S1474-4422(19)30238-8
  7. Lymphocytopenia. National Heart, Lung, and Blood Institute (NHLBI). Accessed June 7, 2022. www.nhlbi.nih.gov/health-topics/lymphocytopenia
  8. Steinman L, Comi G, Bar-Or A, et al. P1031. Poster presented at: 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); September 11-13, 2019; Stockholm, Sweden.
References:
  1. ZEPOSIA. Prescribing information. Celgene Corporation, a Bristol Myers Squibb company; 2022.
  2. Spiegel S, Milstien S. The outs and the ins of sphingosine-1-phosphate in immunity. Nat Rev Immunol. 2011;11(6):403-415. doi:10.1038/nri2974
  3. Choi JW, Gardell SE, Herr DR, et al. FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci U S A. 2011;108(2):751-756. doi:10.1073/pnas.1014154108
  4. Prager B, Spampinato SF, Ransohoff RM. Sphingosine 1-phosphate signaling at the blood–brain barrier. Trends Mol Med. 2015;21(6):354-363. doi:10.1016/j.molmed.2015.03.006
  5. Li N, Zhang F. Implication of sphingosin-1-phosphate in cardiovascular regulation. Front Biosci (Landmark Ed). 2016;21:1296-1313. doi:10.2741/4458
  6. Peyrin-Biroulet L, Christopher R, Behan D, Lassen C. Modulation of sphingosine-1-phosphate in inflammatory bowel disease. Autoimmun Rev. 2017;16(5):495-503. doi:10.1016/j.autrev.2017.03.007
  7. Olesch C, Ringel C, Brune B, Weigert A. Beyond immune cell migration: the emerging role of the sphingosine-1-phosphate receptor S1PR4 as a modulator of innate immune cell activation. Mediators Inflamm. 2017;2017:6059203. doi:10.115/2017/6059203
  8. Scott FL, Clemons B, Brooks J, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173(11):1778- 1792. doi:10.1111/bph.13476
Reference:
  1. ZEPOSIA. Prescribing information. Celgene Corporation, a Bristol Myers Squibb company; 2022.
IMPORTANT SAFETY INFORMATION
Contraindications:
  • Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • Patients with severe untreated sleep apnea
  • Patients taking a monoamine oxidase (MAO) inhibitor
Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA.
  • Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.
  • Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
  • In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.
  • Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.
Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability.
PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.
If confirmed, treatment with ZEPOSIA should be discontinued.
Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:
  • with significant QT prolongation
  • with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
  • with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
  • with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block
Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease.
Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com.
Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA.
Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated.
Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued.
Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued.
Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended.
Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation.
Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA.
Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache.
Use in Specific Populations: Hepatic Impairment: Use is not recommended.
For additional safety information, please see the full Prescribing Information and Medication Guide
INDICATIONS
ZEPOSIA® (ozanimod) is indicated for the treatment of:
  1. Moderately to severely active ulcerative colitis (UC) in adults.
  2. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

References:

  1. ZEPOSIA. Prescribing Information, Celgene Corporation, a Bristol Myers Squibb company.
  2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022. 
  3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.

References:

  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company.
  2. Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280-1291.
  3. Sandborn WJ, Feagan BG, D’Haens G, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis [supplementary appendix]. N Engl J Med. 2021;385(14):1280-1291.
  4. Danese S, Colombel JF, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Oral Presentation at: ECCO 2022; February 16-19, 2022. Presentation DOP44.
  5. Data on file. BMS-REF-OZA-022. Princeton, NJ; Bristol-Myers Squibb Company; 2022.
  6. Sandborn WJ, Feagan BG, Hanauer S, et al. Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, phase 2 TOUCHSTONE study. J Crohns Colitis. 2021;15:1120-1129.
  7. Long M, Cross R, Calkwood J, et al. Ozanimod first-dose cardiac effects in patients with moderately to severely active ulcerative colitis and relapsing multiple sclerosis. Poster presented at AIBD 2021; December 9-11, 2021.

References:

  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol-Myers Squibb Company.
  2. Data on file. BMS-REF-OZA-0022. Princeton, NJ. Bristol-Myers Squibb Company; 2022
  3. Danese S, Colombel J-F, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Oral presentation at: 17th Congress of the European Crohn’s and Colitis Organization; February 16-19, 2022; Virtual. Session DOP44.
  4. Sanborn WJ, Feagan BG, Hanauer S, et al. Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, phase 2 TOUCHSTONE Study. J Crohns Colitis. 2021;15(7):1120-1129.
  5. Siegmund B, Axelrad J, Pondel M, et al. Rapidity of ozanimod-induced symptomatic response and remission in patients with moderately to severely active ulcerative colitis: results from the induction period of True North. Oral presentation at: ECCO 2022; February 16-19, 2022.
  6. Panaccione R, Afzali A, Hudesman D, et al. Extended therapy with ozanimod for delayed responders to ozanimod in moderately to severely active ulcerative colitis: data from the True North open-label study. Poster presented at: DDW 2022; May 21-24, 2022.
  7. Sandborn WJ, Feagan BG, D’Haens G, et al; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis [supplementary appendix]. N Engl J Med. 2021;385:1280-1291.

References:

  1. Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2020;8:CD000543.
  2. Khan N, Abbas A, Williamson A, Balart L. Prevalence of corticosteroids use and disease course after initial steroid exposure in ulcerative colitis. Dig Dis Sci. 2013;58:2963-2969.
  3. Burri E, Maillard MH, Schoepfer AM, et al. Treatment algorithm for mild and moderate-to-severe ulcerative colitis: an update. Digestion. 2020;101 Suppl 1:2-15.
  4. Rubin DT, Sninsky C, Siegmund B, et al. International perspectives on management of inflammatory bowel disease: opinion differences and similarities between patients and physicians from the IBD GAPPS survey. Inflamm Bowel Dis. 2021;27(12):1942-1953.
  5. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company.
  6. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  7. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.

References:

  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company.
  2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.

References:

  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol-Myers Squibb Company.
  2. Data on file. BMS-REF-OZA-0016. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  3. Data on file. BMS-REF-OZA-0017. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Danese S, Colombel J-F, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Oral presentation at: 17th Congress of the European Crohn’s and Colitis Organization; February 16-19, 2022; Virtual. Session DOP44.
  5. Sandborn WJ, Feagan BG, D’Haens G, et al; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385:1280-1291.
  6. Rieder F, Wolf DC, Charles L, Kollengode K, Patel A, Ghosh S. Incidence of infections in patients with moderately to severely active ulcerative colitis treated with ozanimod and relationship to significant lymphopenia: results from a pooled safety analysis. Poster presented at: DDW 2021 Virtual Digestive Disease Week; May 21-23, 2021.
  7. Danese S, Feagan BG, Wolf DC, et al. Ozanimod as maintenance therapy in patients with moderate-to-severe ulcerative colitis: results from the phase 3, randomized, double-blind, placebo-controlled TRUE NORTH Study. Oral Presentation at: UEG Week; October 11-13, 2020. Presentation LB10.
  8. D’Haens G, Colombel JF, Lichtenstein GR, et al. Safety of ozanimod in patients with moderately to severely active ulcerative colitis over time: pooled analysis from phase 2, phase 3, and open-label extension trials. Oral presentation at: DDW 2021 Virtual Digestive Disease Week; May 21–23, 2021.
  9. Data on file. BMS-REF-OZA-0020. Princeton, NJ: Bristol-Myers Squibb Company; 2022.

References:

  1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company.
  2. Danese S, Furfaro F, Vetrano S. Targeting S1P in inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration. J Crohns Colitis. 2018;12(suppl 2):S678-S686.
  3. Peyrin-Biroulet L, Christopher R, Behan D, Lassen C. Modulation of sphingosine-1-phosphate in inflammatory bowel disease. Autoimmune Rev. 2017;16:495-503.
  4. Suh JH, Saba JD. Sphingosine 1-phosphate in inflammatory bowel disease and colitis-associated colon cancer: the fat's in the fire. Transl Cancer Res. 2015;4(5):469-483.
  5. Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol. 2007;8:1295-1301.
  6. Jaigirdar SA, Benson RA, Elmesmari A, et al. Sphingosine-1-phosphate promotes the persistence of activated CD4 T cells in inflamed sites. Front Immunol. 2017;8:1627.
  7. Karuppuchamy T, Behrens E-H, González-Cabrera P, et al. Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease. Mucosal Immunol. 2017;10:162-171.
  8. Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science. 2005;309:1735-1739.
  9. Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015;125:1379-1387.
  10. Roviezzo F, Brancaleone V, De Gruttola L, et al. Sphingosine-1-phosphate modulates vascular permeability and cell recruitment in acute inflammation in vivo. J Pharmacol Exp Ther. 2011;337:830-837.
  11. Lamb YN. Ozanimod: first approval. Drugs. 2020;80(8):841-848.
  12. Lucaciu LA, Seicean R, Seicean A. Small molecule drugs in the treatment of inflammatory bowel diseases: which one, when and why? — a systematic review. Eur J Gastroenterol Hepatol. 2020;32:669-677.
  13. Scott FL, Clemons B, Brooks J, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173:1778-1792.

References:

  1. ZEPOSIA. Prescribing Information, Celgene Corporation, a Bristol Myers Squibb company.
  2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.
  4. Data on File. BMS-REF-OZA-023. Princeton, NJ: Bristol-Myers Squibb Company; 2021.
IMPORTANT SAFETY INFORMATION
INDICATIONS
ZEPOSIA® (ozanimod) is indicated for the treatment of:
  1. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
  2. Moderately to severely active ulcerative colitis (UC) in adults.
IMPORTANT SAFETY INFORMATION
Contraindications:
  • Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • Patients with severe untreated sleep apnea
  • Patients taking a monoamine oxidase (MAO) inhibitor
Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA.
  • Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.
  • Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
  • In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.
  • Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.
Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability.

PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.

If confirmed, treatment with ZEPOSIA should be discontinued.

Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:
  • with significant QT prolongation
  • with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
  • with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
  • with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block
Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease.
Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com.
Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA.
Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated.
Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued.
Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued.
Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended.
Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation.
Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA.
Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache.

Use in Specific Populations: Hepatic Impairment: Use is not recommended.
For additional safety information, please see the full Prescribing Information and Medication Guide
This site is intended for U.S. Healthcare Professionals only.
ZEPOSIA, ZEPOSIA 360 Support and ZEPOSIA logo are trademarks of Celgene
Corporation, a Bristol Myers Squibb company.
All other trademarks are the property of their respective owners.
All other trademarks are the property of their respective owners.
© 2022 2022 Bristol-Myers Squibb Company. 2084-US-2201402 09/22
2084-US-2201774 12/22
2084-US-2201400 11/22

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