b'B:8.75"T:8.25"S:7.25"ZEPOSIA(ozanimod) capsules, for oral use In UC Study 1 and Study 3, herpes zoster was reported in 0.4% of patients who received ZEPOSIA (ozanimod) and none in patients who received placebo. In UC Study 2, herpes zoster was reported in 2.2% of patients who received ZEPOSIA and 0.4% of patients who received placebo. None were serious or disseminated.Brief Summary of Prescribing Information. For complete prescribinginformation consult officialHerpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate packageinsert. (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 INDICATIONS AND USAGE antibodies to VZV before initiating ZEPOSIA (see Vaccinations below).ZEPOSIA (ozanimod) is indicated for the treatment of: Cryptococcal Infectionmoderately to severely active ulcerative colitis (UC) in adults. Cases of fatal cryptococcal meningitis (CM) and disseminated cryptococcal infections have been reported with S1P receptor modulators. Physicians should be vigilant for clinical symptoms or signs of CM. Patients with symptoms DOSAGE AND ADMINISTRATION or signs consistent with a cryptococcal infection should undergo prompt diagnostic evaluation and treatment. Assessments Prior to First Dose of ZEPOSIA ZEPOSIA treatment should be suspended until a cryptococcal infection has been excluded. If CM is diagnosed, Before initiation of treatment with ZEPOSIA, assess the following: appropriate treatment should be initiated.Complete Blood Count Progressive Multifocal LeukoencephalopathyProgressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the brain caused by the Obtain a recent (i.e., within the last 6 months or after discontinuation of prior UC therapy) complete blood countJC virus (JCV) that typically occurs in patients who are immunocompromised, and that usually leads to death or (CBC), including lymphocyte count [see Warnings and Precautions]. severe disability. Typical symptoms associated with PML are diverse, progress over days to weeks, and include Cardiac Evaluation progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.Obtain an electrocardiogram (ECG) to determine whether preexisting conduction abnormalities are present. In patients with certain preexisting conditions, advice from a cardiologist should be sought [see Warnings andPML has been reported in patients treated with S1P receptor modulators and other UC therapies and has been Precautions]. associated with some risk factors (e.g., immunocompromised patients, polytherapy with immunosuppressants). Physicians should be vigilant for clinical symptoms or MRI findings that may be suggestive of PML. MRI findings Liver Function Tests may be apparent before clinical signs or symptoms. If PML is suspected, treatment with ZEPOSIA should be Obtain recent (i.e., within the last 6 months) transaminase and bilirubin levels [see Warnings and Precautions]. suspended until PML has been excluded by an appropriate diagnostic evaluation.Ophthalmic Assessment If PML is confirmed, treatment with ZEPOSIA should be discontinued.In patients with a history of uveitis or macular edema, obtain an evaluation of the fundus, including the maculaPrior and Concomitant Treatment with Anti-Neoplastic, Non-Corticosteroid Immunosuppressive, or Immune-[see Warnings and Precautions]. modulating TherapiesCurrent or Prior Medications In UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with anti-neoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for the treatment If patients are taking anti-neoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies,of UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressiveimmunosuppression. In UC studies, concomitant use of corticosteroids was allowed and did not appear to effects before initiating treatment with ZEPOSIA [see Warnings and Precautions and Drug Interactions]. influence the safety or efficacy of ZEPOSIA [see Clinical Studies (14.2) in full Prescribing Information].Determine if patients are taking drugs that could slow heart rate or atrioventricular conduction [see WarningsAnti-neoplastic, immune-modulating, or immunosuppressive therapies (including corticosteroids) should be co-and Precautions and Drug Interactions]. administered with caution because of the risk of additive immune system effects during such therapy. When Vaccinations switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.Test patients for antibodies to varicella zoster virus (VZV) before initiating ZEPOSIA; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment with ZEPOSIA [see Warnings and PrecautionsVaccinationsand Drug Interactions]. If live attenuated vaccine immunizations are required, administer at least 1 month prior toPatients without a healthcare professional-confirmed history of chickenpox or without documentation of a full initiation of ZEPOSIA. course of vaccination against VZV should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of Recommended Dosage for Ulcerative Colitis vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment Initiate ZEPOSIA with a 7-day titration, as shown in Table 1 [see Warnings and Precautions]. After initial titration, thewith ZEPOSIA, following which initiation of treatment with ZEPOSIA should be postponed for 4 weeks to allow the recommended dosage of ZEPOSIA is 0.92 mg taken orally once daily starting on Day 8. full effect of vaccination to occur.Swallow ZEPOSIA capsules whole, with or without food [see Clinical Pharmacology (12.3) in full PrescribingNo clinical data are available on the efficacy and safety of vaccinations in patients taking ZEPOSIA. Vaccinations Information]. may be less effective if administered during ZEPOSIA treatment.If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA. Table 1:Dose Titration Regimen Avoid the use of live attenuated vaccines during and for 3 months after treatment with ZEPOSIA. S:9.875" T:10.875" B:11.375"Days 1-4 0.23 mg once daily Bradyarrhythmia and Atrioventricular Conduction DelaysDays 5-7 0.46 mg once daily Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, an up-titration scheme should be used to reach the maintenance dosage of ZEPOSIA [see Dosage and Day 8 and thereafter 0.92 mg once daily Administration and Clinical Pharmacology (12.2) in full Prescribing Information].ZEPOSIA was not studied in patients who had:Reinitiation of ZEPOSIA after Treatment Interruption A myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization If a dose of ZEPOSIA is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimenwithin the last 6 months[see Dosage and Administration]. New York Heart Association Class III / IV heart failureIf a dose of ZEPOSIA is missed after the first 2 weeks of treatment, continue with the treatment as planned. Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF 450 msec in males, 470 msec in females), risk factors for QT prolongation, or other conduction CONTRAINDICATIONS abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patients ZEPOSIA is contraindicated in patients who: healthIn the last 6 months, have experienced a myocardial infarction, unstable angina, stroke, transient ischemicOther pre-existing stable cardiac conditions without clearance from a cardiologistattack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure [see WarningsSevere untreated sleep apneaand Precautions] A resting heart rate less than 55 beats per minute (bpm) at baselineHave the presence of Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinusReduction in Heart Ratesyndrome, or sino-atrial block, unless the patient has a functioning pacemaker [see Warnings and Precautions] Initiation of ZEPOSIA may result in a transient decrease in heart rate. After the initial dose of ZEPOSIA 0.23 mg, Have severe untreated sleep apnea [see Warnings and Precautions] the greatest mean decrease from baseline in heart rate occurred at Hour 5 on Day 1 (0.7 bpm in UC Study 1 Are taking a monoamine oxidase (MAO) inhibitor [see Drug Interactions] and Study 3), returning to near baseline at Hour 6. With continued up-titration, the maximal heart rate effect of ozanimod occurred on Day 8. The utility of performing first-dose cardiac monitoring when initiating ZEPOSIA in WARNINGS AND PRECAUTIONS patients with characteristics similar to those studied in the clinical trials of ZEPOSIA is unclear. Heart rates below Infections 40 bpm were not observed. Initiation of ZEPOSIA without titration may result in greater decreases in heart rate [see Risk of Infections Dosage and Administration].ZEPOSIA causes a mean reduction in peripheral blood lymphocyte count to approximately 45% of baseline valuesIn UC Study 1 and Study 3, bradycardia was reported on the day of treatment initiation in 1 patient (0.2%) treated with ZEPOSIA compared to none in patients who received placebo. After Day 1, bradycardia was reported in 1 because of reversible sequestration of lymphocytes in lymphoid tissues [see Clinical Pharmacology (12.2) in fullpatient (0.2%) treated with ZEPOSIA. In UC Study 2, bradycardia was not reported.Prescribing Information]. ZEPOSIA may therefore increase the susceptibility to infections, some serious in nature. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Atrioventricular Conduction DelaysObtain a recent (i.e., within 6 months or after discontinuation of prior UC therapy) complete blood count (CBC)Initiation of ZEPOSIA may result in transient atrioventricular conduction delays. At ZEPOSIA exposures higher than including lymphocyte count before initiation of ZEPOSIA. the recommended dosage without dose titration, first- and second-degree type 1 atrioventricular blocks were Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. observed in healthy volunteers; however, in UC Study 1 and Study 3 with dose titration, Mobitz type 2 second- or third-degree atrioventricular blocks were not reported in patients treated with ZEPOSIA.In UC Study 1 and Study 3, the overall rate of infections and rate of serious infections in patients treated withIf treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:ZEPOSIA were similar to that in patients who received placebo (9.9% vs. 10.7% and 0.8% vs. 0.4%, respectively). In UC Study 2, the overall rate of infections in patients treated with ZEPOSIA was higher than in patients treatedWith significant QT prolongation (QTcF 450 msec in males, 470 msec in females)with placebo (23% vs. 12%) and the rate of serious infections was similar (0.9% vs. 1.8%). With arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugsZEPOSIA increased the risk of viral upper respiratory tract infections, urinary tract infections, and herpes infectionsWith ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular [see Adverse Reactions]. disease, and uncontrolled hypertensionThe proportion of patients treated with ZEPOSIA with lymphocytes less than 0.2 x 109/L was 2% in UC Study 1With a history of with second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sinoatrial heart and Study 3 and 2.3% in UC Study 2. These values generally returned to greater than 0.2x109/L while patientsblock [see Contraindications]remained on treatment with ZEPOSIA. After discontinuing ZEPOSIA 0.92 mg, the median time for peripheral bloodLiver Injurylymphocytes to return to the normal range was approximately 30days, with approximately 80% to 90% of patients in the normal range within 3 months [see Clinical Pharmacology (12.2) in full Prescribing Information]. Elevations of aminotransferases may occur in patients receiving ZEPOSIA.Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection.Obtain transaminase and bilirubin levels, if not recently available (i.e., within 6 months), before initiation Because the elimination of ZEPOSIA after discontinuation may take up to 3 months, continue monitoring forof ZEPOSIA.infections throughout this period. In UC Study 1, elevations of ALT to 5-fold the ULN or greater occurred in 0.9% of patients treated with ZEPOSIA Herpes Viral Infection 0.92 mg and 0.5% of patients who received placebo, and in UC Study 2 elevations occurred in 0.9% of patients and no patients, respectively. In UC Study 1, elevations of ALT to 3-fold the ULN or greater occurred in 2.6% of UC Cases of localized herpes virus infection (e.g., herpes zoster and herpes simplex) were seen in clinical trialspatients treated with ZEPOSIA 0.92 mg and 0.5% of patients who received placebo, and in UC Study 2 elevations of ZEPOSIA. occurred in 2.3% of patients and no patients, respectively. In controlled and uncontrolled UC studies, the majority Cosmos Communications 1 Q1 Q2K ej44878b 07.14.21 133 1 Cosmos Communications 1 Q1 Q2K ej44878a 07.13.21 133 1PREPARED BY 11561844 US Branded Journal Ad A SIZE M25FRJob info Images FontsSpecial InstructionsDate: 7-1-2021 6:46 PM 2084_US_2100924_ZEPOSIA UC PBSNone 3 PG 4/C ad: spread followed by single page-Client: BMS 7x9.875_0521_wip2FNL.pdf (98%; 78KB) Create 5 pgs blank or greeked Brief Summary Product: OZANIMOD US pages for nowBuild mech to final A size specs Client Code: 2084-US-2101341 Additional InformationWF Issue # 8935889 NoneReleasing as: Native FilesFinal Size: NoneFinishing: NoneGutter: None Inks Additional Comments for SizingColors: 4/C & B/WBlack Single page 4/C specs: 8.25in x 10.875inLIVE: 7.25in*x 10in (.50 from trim edge)BLEED: 8.50in Team x 11.375inProducer: NoneAD: Phoebe FelizAE: Leah OKeeffe Scale: 1"= 1"QC: None Bleed 17" w x 11.375" h 17" w x 11.375" hProduction: Debi Post Trim/Flat 16.5" w x 10.875" h 16.5" w x 10.875" hDigital Artist: Eberhart, Thomas (NYC-FCB) Live/Safety 15.5" w x 9.875" h 15.5" w x 9.875" h FR Spellcheck:NonePath: PrePress:BMS:OZANIMOD:11561844:11561844_US_Branded_Ad_M25FR.indd_ _'