b'B:17"T:16.25"S:15.25"FOR YOUR PATIENTS WITH RMS 1PROTECT IT BEFORE ITS GONEWITH ZEPOSIA, YOU HAVE THE POWER TO HELP PRESERVE THEIR MOST VALUABLE RESOURCE1Powerful effi cacy in reducing ARR, GdE lesions, and new/enlarging T2 lesions vs Avonex 1aData on brain volume and cognitiveSafety comparable to Avonex in overall processing speed (SDMT) inincidence of adverse reactions 2,3csecondary, exploratory endpointsand generally similar safety demonstrated and post hoc analysis 2,3b in the long-term extension study4da Study 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-g 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 con rmed 3-month disability progression. There was no signi cant difference in 3-month con rmed disability between ZEPOSIA and Avonex. 1-3b S:9.875" T:10.5" B:11.375"Brain volume loss was analyzed as secondary (whole brain volume loss) and exploratory endpoints (thalamic volume loss and cortical grey matter volume loss) in the SUNBEAM and RADIANCE trials. Volume loss endpoints werenot part of the statistical analysis hierarchy. SDMT is a tool that measures cognitive processing speed and was analyzed in a post hoc analysis of SUNBEAM and DAYBREAK, an ongoing open-label extension study. The MSFC was a secondary endpoint made up of 3 components: 9-hole peg test (arm/hand function), timed 25-foot walk (ambulation), and SDMT (cognitive function). SUNBEAM SDMT post hoc: ZEPOSIA (n=427), Avonex (n=426) at Month 12. DAYBREAK SDMT post hoc (SUNBEAM participants only): ZEPOSIA (n=376) at Month 42. SDMT was not part of the statistical analysis hierarchy for SUNBEAM and was analyzed descriptively in DAYBREAK.c Adverse 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 INDICATION infection, 26% (vs 23%); hepatic transaminase elevation, 10% (vs 5%); orthostatic hypotension, 4% (vs 3%); urinary tract infection, 4% ZEPOSIA (ozanimod) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include(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 clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.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-IMPORTANT SAFETY INFORMATION 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 Contraindications: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% Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transientfor Avonex and the rate at 2 years for ZEPOSIA was 6.5% vs 6.4% for Avonex.Please see full Prescribing Information for additional 1-3ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failureSUNBEAM and RADIANCE data. or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sickd Study design: DAYBREAK is an ongoing open-label extension (OLE) trial that enrolled participants from multiple randomized phase sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker 1 to 3 studies, including SUNBEAM and RADIANCE. These data are presented as an interim analysis with a data cutoff of February 2,Patients with severe untreated sleep apnea 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,Patients taking a monoamine oxidase (MAO) inhibitor and GdE lesions. Endpoints were analyzed descriptively. 4,5Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infectionsTreatment-emergent adverse events (TEAEs): At the data cutoff (up to 5 years), the overall incidence of TEAEs for ZEPOSIA in the have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuationDAYBREAK 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, of prior MS therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA.8.9%; lymphopenia, 8.7%; back pain, 8.1%; gamma-glutamyl transferase increased, 5.9%; bronchitis, 5.8%; urinary tract infection, 5.8%; Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Considerhypertension, 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%. interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for4infections up to 3 months after discontinuing ZEPOSIA. Serious TEAEs: The rate of serious TEAEs was 11.7%.ALC=absolute lymphocyte count; ARR=annualized relapse rate; GdE=gadolinium enhancing; MSFC=Multiple Sclerosis Functional Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitisComposite; RMS=relapsing multiple sclerosis; SDMT=Symbol Digit Modalities Test.and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-con rmed 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 withPlease see Important Safety Information throughout and Brief Summary of full Prescribing Information.varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.Start at ZEPOSIAhcp.com/MSPREPARED BY11707081 BMS_MS_Spread Journal Ad - A-size M7FR11707081_BMS_MS_Spread Journal Ad_Asize_M7FR.indd 1 Job info Images FontsSpecial Instructions 3/19/22 11:09 AMDate: 3-19-2022 11:06 AM BMS_A077567_4C.tif (CMYK; 361 ppi; 82.91%;Montserrat (Regular, Bold, Medium, SemiBold),NoneClient: BMS 305.7MB), ZEPOSIA_US_TM_OD_CMYK_FC_Pos. Arial Narrow (Regular)Product: ZEPOSIA ai (35.74%; 71KB)Client Code: None Additional InformationWF Issue # None NoneReleasing as: PDFx1AFinal Size:Finishing: NoneGutter: None Inks Additional Comments for SizingColors: NoneCyan, Magenta, Yellow, Black NoneTeam 4CProducer: Jessica SbailoAD: Joe MaranzinoAE: Carin Caselli Scale: 1"= 1"QC: None Bleed 16.25" w x 10.5" h16.25" w x 10.5" hProduction: Steve Curry Trim/Flat 16.25" w x 10.5" h16.25" w x 10.5" hDigital Artist: Kolosick, Tanya (NYC-SRX) Live/Safety 15.25" w x 9.875" h15.25" w x 9.875" h Path: PrePress:BMS:OZANIMOD:11707081:_Packaged_Jobs:11707081_BMS_MS_Spread Journal Ad_Asize_M7FR:11707081_BMS_MS_Spread Journal Ad_Asize_M7FR.inddPDFX1A _'