ZEPOSIA has been studied across multiple indications in 4 clinical trials, including TRUE NORTH (NCT02435992), a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial; TOUCHSTONE (NCT01647516), a randomized, double-blind, placebo-controlled phase 2 clinical trial; and SUNBEAM (NCT02294058) and RADIANCE (NCT02047734), 2 multicenter, randomized, double-blind, double-dummy, active treatment-controlled phase 3 clinical trials. 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.1
aAdditional data from the induction period of a randomized, double-blind, placebo-controlled study [UC Study 3/TOUCHSTONE] included 67 patients who received ZEPOSIA 0.92 mg once daily.1
bIncludes the following terms: streptococcal pharyngitis, pharyngotonsillitis, bacterial pharyngitis, nasopharyngitis, upper respiratory tract infection, pharyngitis, sinusitis, tonsillitis, viral upper respiratory tract infection, laryngitis, acute sinusitis, catarrh, chronic sinusitis, upper respiratory tract inflammation, chronic tonsillitis, viral pharyngitis, viral sinusitis, bacterial sinusitis, bacterial upper respiratory tract infection, viral labyrinthitis, laryngeal inflammation, and pharyngeal inflammation.1
cIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, liver function test increased, blood alkaline phosphatase increased, transaminases increased.1
dZEPOSIA was initiated with a 7-day titration.1
ePercentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.1
aIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, blood bilirubin increased, liver function test increased, blood alkaline phosphatase increased.1
ALT=alanine aminotransferase; LFT=liver function test; ULN=upper limit of normal.
In controlled and uncontrolled clinical trials with ZEPOSIA, mean lymphocyte counts decreased to approximately 45% of baseline at 3 months (approximate mean blood lymphocyte counts 0.8 x 109/L), and low lymphocyte counts were maintained during treatment with ZEPOSIA.1
Pooled Analysis of Controlled and Uncontrolled Trials
aPatients may be included in both placebo and ZEPOSIA treatment groups. The total count in the placebo group includes 227 patients who were treated with ZEPOSIA in the induction period and were re-randomized to placebo in the maintenance period of TRUE NORTH.2
Overall Discontinuation Rates3,4
UC Study 1—Induction: 6% for ZEPOSIA | 11% for Placebo
UC Study 2—Maintenance: 20% for ZEPOSIA | 45% for Placebo
aAdditional data from the induction period of a randomized, double-blind, placebo-controlled study (UC Study 3/TOUCHSTONE) included 67 patients who received ZEPOSIA 0.92 mg once daily.1
aTotal patient-years equals the sum of the number of years on study contributed by each patient from time of first dose per treatment group in the pool to last date on study per treatment group in the pool. The algorithm for the last date on study is dependent on patient disposition and whether the patient enrolled into an extension study.5
bIncidence rate per 100 patient-years, calculated as number of patients/PY x 100 for specific SOC category or PT subcategory. Analysis was based on the treatment group to which a patient was assigned when the event occurred, including patients who were re-randomized to placebo.5
cTOUCHSTONE patients randomized to ZEPOSIA 0.46 mg unapproved dose were only analyzed upon entering TOUCHSTONE OLE and receiving daily ZEPOSIA 0.92 mg.5
IR=incidence rate; OLE=open-label extension; PT=preferred term; PY=patient years; S1P=sphingosine 1-phosphate; SOC=system organ class.
Learn about the mechanism of action for ZEPOSIA, the first and only sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active UC in adults1
References: 1. ZEPOSIA. Prescribing Information. Bristol-Myers Squibb Company; 2021. 2. 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. 3. Sandborn WJ, D’Haens G, Wolf DC, et al. Ozanimod as induction therapy in 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 LB02. 4. 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. 5. 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.
ZEPOSIA® (ozanimod) is indicated for the treatment of:
IMPORTANT SAFETY INFORMATION
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
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:
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
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 Disability After Stopping ZEPOSIA: 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
For additional safety information, please see the full Prescribing Information and Medication Guide.
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This information is intended for U.S. Healthcare Professionals.