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Nearly a Decade of Clinical Trial Experience Across Multiple Indications1,2a

6 Clinical Trials, ~38,000 ZEPOSIA-Treated Patients Across Multiple Indications, >40,000 patient years of total exposure in clinical trials 6 Clinical Trials, ~38,000 ZEPOSIA-Treated Patients Across Multiple Indications, >40,000 patient years of total exposure in clinical trials

Overall ZEPOSIA 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 ZEPOSIA in parent and extension trials (all indications) was 3789 and estimated to be 34,910 in the post-marketing setting. All trials had a data cutoff of May 19, 2023, and all post-marketing data had a cutoff date of April 30, 2023.10,11

aIn UC, from the start of the TOUCHSTONE phase 2 clinical trial (December 26, 2012) through TRUE NORTH OLE study data cutoff (January 10, 2022). In MS, from the start of the RADIANCE phase 2 clinical trial (September 18, 2012) through the DAYBREAK OLE data cutoff (February 1, 2022). Only includes patients receiving the 0.92-mg dose of ZEPOSIA.2,5,12,13

bZEPOSIA has been studied across multiple indications in 6 phase 2-3 clinical trials1-9:

Moderate-to-severe UC: TRUE NORTH (NCT02435992), a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial; TRUE NORTH OLE (NCT02531126), an ongoing phase 3, multicenter, open-label extension trial; TOUCHSTONE (NCT01647516), a phase 2, multicenter, randomized, double-blind, placebo-controlled trial.2,6-8

Relapsing MS: SUNBEAM (NCT02294058) and RADIANCE (NCT02047734), phase 3, multicenter, randomized, double-blind, double-dummy, active treatment-controlled studies; DAYBREAK (NCT02576717), an ongoing phase 3, multicenter, open-label extension trial.1,3,4,9,13

ZEPOSIA
Demonstrated
Safety Profile1,2

Adverse Reactions With an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at
Least 1% Greater Than Placebo in Patients With Ulcerative Colitis
(Pooled Induction Periods UC Study 1 and Study 3)1c
Adverse Reaction
ZEPOSIA 0.92 mg
(n=496)fg
Placebo
(n=281)g
Upper Respiratory Infectiond 5% 4%
Liver Test Increasede 5% 0%
Headache 4% 3%
Pyrexia 3% 2%
Nausea 3% 2%
Arthralgia 3% 1%

UC Study 3 (8-week induction): TOUCHSTONE is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the clinical efficacy and safety of induction therapy with RPC1063 in 199 patients with moderately to severely active ulcerative colitis. Participants who completed the induction period and were responders at Week 8 continued to receive the same dose of ozanimod during the maintenance period up to Week 32.

For full study design of UC Study 1 and Study 2, click here.

  • cAdditional 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
  • dIncludes 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
  • eIncludes 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
  • fZEPOSIA was initiated with a 7-day titration.1
  • gPercentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.1
Adverse Events from TRUE NORTH (UC Study 1) Induction Period6
ZEPOSIA 0.92 mg
(n=429)
Placebo
(n=216)
Adverse Event 40.1% 38%
Serious Adverse Event 4% 3.2%
Adverse Reactions With an Incidence of at Least 4% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With Ulcerative Colitis (UC Study 2)
Maintenance Period1
Adverse Reaction
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
Liver Test Increasedh 11% 2%
Headache 5% <1%
  • hIncludes 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
Adverse Events from TRUE NORTH (UC Study 2) Maintenance Period6
ZEPOSIA 0.92 mg
(n=230)
Placebo
(n=227)
Adverse Event 49.1% 36.6%
Serious Adverse Event 5.2% 7.9%
In ZEPOSIA-treated patients, rates of thromboembolic events or major adverse cardiac events were similar to patients treated with placebo in TRUE NORTH.14ij
  • iIn the TRUE NORTH Phase 3 studies, 1 case of ischemic stroke (0.2%) was reported in ZEPOSIA-treated patients versus no reports in patients treated with placebo.14
  • jThromboembolic events include pulmonary embolism and venous arterial thrombosis. Major or adverse cardiac events include cardiovascular death, myocardial infarction, and stroke. 14

MS=multiple sclerosis; OLE=open-label extension; UC=ulcerative colitis.

UC Study 1 and Study 2
Adverse Reaction
Induction
Maintenance
 ZEPOSIA
0.92 mg
(n=429)		 Placebo
(n=216)		 ZEPOSIA
0.92 mg
(n=230)		 Placebo
(n=227)
ALT ≥3x ULN
 2.6% 0.5% 2.3% 0%
ALT ≥5x ULN
 0.9% 0.5% 0.9% 0%
  • In controlled and uncontrolled UC studies, the majority (96%) of patients with ALT >3X ULN continued treatment with ZEPOSIA, with values returning to <3X ULN within ~2-4 weeks1
  • The overall discontinuation rate because of elevations in hepatic enzymes was 0.4% in patients treated with ZEPOSIA 0.92 mg and none in patients who received placebo in the controlled UC studies1
  • Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine, should have hepatic enzymes checked, and ZEPOSIA should be discontinued if significant liver injury is confirmed1

ALT=alanine aminotransferase; LFT=liver function test; UC=ulcerative colitis; ULN=upper limit of normal.

In controlled 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

  • The proportion of patients treated with ZEPOSIA with lymphocytes less than 0.2 x 109/L was 2.0% in UC Study 1 and Study 3 (phase 2) and 2.3% in UC Study 21
  • These values generally returned to greater than 0.2 x 109/L while patients remained on treatment with ZEPOSIA1
  • After discontinuing treatment, the median time for peripheral blood lymphocytes to return to the normal range was approximately 30 days1
    • Approximately 80% to 90% of patients were in the normal range within 3 months1
Pooled Analysis of Controlled and Uncontrolled Trials15
Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit
  • Descriptive pooled analysis of controlled and uncontrolled trials including the 32-week phase 2 TOUCHSTONE trial, the 52-week phase 3 TRUE NORTH trial, and an open-label extension study. Patients completing ≥1 year of the TOUCHSTONE OLE could roll over into the TRUE NORTH OLE15
  • Reductions in ALC were observed at Week 5 (the first post-baseline assessment) and sustained through treatment15
  • 60 patients (5.3%) had ALC <0.2 x 109/L at least once during ZEPOSIA treatment15
    • Most patients (98.3%; n=59) returned to ALC ≥0.2 x 109/L at the time of the analysis; 89.8% returned to ≥0.2 x 109/L while continuing treatment with ZEPOSIA15
  • kPatients 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.15

ALC=absolute lymphocyte count; OLE=open-label extension; UC=ulcerative colitis.

Low Discontinuation Rates

Discontinuation Rates Due
to TEAEs That Are Comparable
to Placebo6

Overall Discontinuation Rates6

UC Study 1—Induction:
6.5% for ZEPOSIA | 11.1% for Placebo

UC Study 2—Maintenance:
20.0% for ZEPOSIA | 45.4% for Placebo

Discontinuation Rates Due
to Treatment-Emergent
Adverse Events (TEAEs)6

Induction

3.3%
ZEPOSIA

vs 3.2%
for placebo

Maintenance

1.3%
ZEPOSIA

vs 2.6%
for placebo

One case of macular edema was reported during the maintenance phase in 1 person with preexisting risk factors at baseline; it resolved after discontinuation of treatment.1,16

Overall, the discontinuation rate because of elevations in hepatic enzymes was 0.4% in patients treated with ZEPOSIA 0.92 mg and none in patients who received placebo in the controlled UC studies.1

TEAEs=treatment-emergent adverse events; UC=ulcerative colitis.

Infections and Malignancies

Rates of Serious Infection Were Low and Comparable to Placebo in Clinical Trials1

Rates of Serious Infection in
Clinical Trials1
Inductionl
Maintenance
Infection
 ZEPOSIA 0.92 mg
(n=496)		 Placebo
(n=281)		 ZEPOSIA 0.92 mg
(n=230)		 Placebo
(n=227)
Overall Rate of Infection
 9.9% 10.7% 23% 12%
Serious Infections
 0.8% 0.4% 0.9% 1.8%
Herpes Zoster
 0.4% 0% 2.2% 0.4%
  • Malignancies, such as melanoma, basal cell carcinoma, breast cancer, seminoma, cervical carcinoma, and adenocarcinomas, including rectal adenocarcinoma, were reported with ZEPOSIA in controlled trials of multiple sclerosis and UC. An increased risk of cutaneous malignancies has been reported with another S1P receptor modulator1
  • IAdditional 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
Rates of Malignancies in Clinical Trials6
Induction
Maintenance
Malignancies
Malig-
nancies
 ZEPOSIA 0.92 mg
(n=429)		 Placebo
(n=216)		 ZEPOSIA 0.92 mg
(n=230)		 Placebo
(n=227)
Basal Cell
Carcinoma
 0% 0% 0.4% 0%
Rectal Adenocar-
cinoma
 0% 0% 0.4% 0%
Adenocar-
cinoma of
the Colon
 0% 0% 0% 0.4%
Breast
Cancer
 0% 0% 0% 0.4%
Infections and Malignancies Across All UC Trials With ZEPOSIA17
ZEPOSIA 0.92 mg
(n=1158)
PY=1922.5m
Placebo
(n=508)
PY=249.2m
 % (n) IR, per 100 PYn % (n) IR, per 100 PYn
Any
Infection
 29.1 (337) 22.81 14.0 (71) 31.43
Any
Serious
Infection
 2.2 (25) 1.32 1.4 (7) 2.84
Malignan-
cies
 1.0 (12) 0.63 0.4 (2) 0.81
  • Safety outcomes were analyzed using descriptive statistics on pooled data from all controlled and uncontrolled UC trials: participants from 32-week TOUCHSTONE trialo (phase 2), 52-week TRUE NORTH trial (phase 3), and the respective open-label extension trials17
  • Median treatment duration in weeks for ZEPOSIA 0.92 mg and placebo was 65.79 and 17.21, respectively17
  • TEAEs identified in the pooled data from all controlled and uncontrolled UC trials were consistent with the controlled UC trials17
  • mTotal 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.17
  • nIncidence 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.17
  • oTOUCHSTONE patients randomized to ZEPOSIA 0.46 mg unapproved dose were only analyzed upon entering TOUCHSTONE OLE and receiving daily ZEPOSIA 0.92 mg.18

IR=incidence rate; OLE=open-label extension; PT=preferred term; PY=patient-years; S1P=sphingosine 1-phosphate; SOC=system organ class; UC=ulcerative colitis.

Long-Term Safety Data From the TRUE NORTH Open-Label Extension Up to Week 14619,20

This safety analysis includes patients (N=823) with UC from the TRUE NORTH parent study who entered the TRUE NORTH open-label extension for up to 146 weeks of ZEPOSIA exposure19,20

Safety From All TRUE NORTH Patients in OLE (N=823)
Adverse
Events
All Patients in OLE
EAIR per 100 Patient-Yearsp
TEAEs 87.6
Serious TEAEs 7.4
TEAEs Leading to Discontinuation
of ZEPOSIA		 2.5
Most Frequent TEAEs (Occurring in ≥5% of Patients)
Lymphopeniaq 6.4
Anemiaq 4.2
Nasopharyngitis 4.1
Lymphocyte Count Decreasedq 4.0
Alanine Aminotransferase Increasedq 3.6
Arthralgia 3.6
COVID-19 3.0
Headache 3.0
Upper Respiratory Tract Infection 2.7
Gamma-glutamyl Transferase Increasedq 2.6
Hypertension 2.3
UC Exacerbation 2.0
Cough 2.0
Infection (Occuring in ≥3% of Patients) 23.6
Serious Infection 1.9
Nasopharyngitis 4.1
COVID-19 3.0
Upper Respiratory Tract Infection 2.7
Herpes Zoster 1.3
Sinusitis 1.3
Bronchitis 1.2
Influenza 1.2
Malignancyr 0.6
Basal Cell Carcinoma 0.3
Prostate Cancer 0.1
Colon Adenocarcinoma 0.1
Breast Cancer 0.1
Malignant Lung Neoplasm 0.1
Rectal Adenocarcinoma 0.1
Rectal Cancer Stage II 0.1
  • Two deaths were reported during OLE: 1 sudden death and 1 due to COVID-19. Both deaths were deemed to be unrelated to ZEPOSIA treatment by the investigators20

Data cutoff: January 10, 2022.20

  • pTotal PY was defined as the sum of the numbers of years on study contributed by each patient from time of first dose to last date on study; EAIRs were calculated as numbers of patients/PYx1000.12,20
  • qLaboratory values were flagged by the central laboratory if they fell outside the standard reference range. The investigator decided whether the laboratory value qualified as an adverse event.21
  • r Malignancies reported include 6 basal cell carcinomas and 3 colorectal neoplasms.20

EAIR=exposure-adjusted incidence rate; NR=not reported; OLE=open-label extension; SAE=serious adverse event; TEAE=treatment-emergent adverse event; UC=ulcerative colitis; ULN=upper limit of normal.

Explore the Efficacy
Data for ZEPOSIA

Understand the Study
 Design

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.
Immune reconstitution inflammatory syndrome (IRIS) has been reported in MS patients treated with S1P receptor modulators who developed PML and subsequently discontinued treatment. IRIS presents as a clinical decline in the patient’s condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML was generally within a few months after S1P receptor modulator discontinuation. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.
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.
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. After stopping ZEPOSIA in the setting of PML, monitor for development of immune reconstitution inflammatory syndrome (PML-IRIS).
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: Dosage adjustment in patients with mild or moderate hepatic impairment (Child-Pugh class A or B) is required, and use of ZEPOSIA in patients with severe hepatic impairment (Child-Pugh class C) 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. 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(10):29​63-29​69.
  2. 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.
  3. Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(suppl 3):s1-s106.
  4. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  5. Efficacy and safety study of ozanimod in ulcerative colitis (Touchstone). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/record/NCT01647516. Updated May 19, 2021. Accessed May 11, 2022.

References:

  1. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  2. 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(14):1280-1291.
  3. 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(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-0031. Princeton, NJ; Bristol-Myers Squibb Company; 2022.
  6. Data on File. BMS-REF-OZA-0022. Princeton, NJ; Bristol-Myers Squibb Company; 2022.
  7. Wolf DC, Colombel JF, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Poster presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual, May 21-24, 2022. Poster Tu1458.
  8. 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. Bristol-Myers Squibb Company; 2023.
  2. 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; March 2022.
  3. 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(14):1280-1291.
  4. Data on File. BMS-REF-OZA-0042. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  5. Danese S, Abreu MT, Afzali A, et al. Symptomatic improvement and long-term stability of ulcerative colitis symptoms over 3 years of ozanimod treatment. Poster presented at: European Crohn’s and Colitis Organisation (ECCO) 2023: Copenhagen, Denmark; March 1-4, 2023. Poster P719.
  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 extension study. Poster presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual, May 21-24, 2022. Poster Tu1450.
  7. Danese S, Abreu MT, Wolf DC, et al. Efficacy and safety of 3 years of continuous ozanimod treatment: an interim analysis of the True North open-label extension study. Oral presentation at: European Crohn’s and Colitis Organisation (ECCO) 2023: Copenhagen, Denmark; March 1-4, 2023. DOP37.
  8. Data on File. BMS-REF-OZA-0031. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  9. Wolf DC, Colombel JF, Ponich T, et al. Long-term use of ozanimod in patients with moderately to severely active ulcerative colitis. Poster presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual, May 21–24, 2022. Poster Tu1458.
  10. 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.
  11. 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(7):1120-1129.
  12. Panaccione R, Danese S, Wolf DC, et al. Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension. Poster presented at: European Crohn’s and Colitis Organisation (ECCO) 2023; Copenhagen, Denmark; March 1–4, 2023. Poster P405.
  13. Data on File. BMS_ZEP008535. Princeton, NJ: Bristol-Myers Squibb Company; 2022.

References:

  1. Friedman S, Blumberg RS. Inflammatory Bowel Disease. Jameson JL. Harrison's Principles of Internal Medicine. Vol 2. Ed 20. McGraw-Hill Education; 2017:2263.
  2. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389(10080):1756-1770.
  3. 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.
  4. 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(10):29​63-29​69.
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  8. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  9. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.

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  2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.

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  14. Long M, Cross RK, Lichtenstein GR, et al. Long-term cardiac safety of ozanimod in phase 3 clinical program of ulcerative colitis and relapsing multiple sclerosis. Presented at: Digestive Disease Week (DDW); San Diego, CA, and Virtual, May 21–24, 2022. Presentation 15.
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References:

  1. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022.
  3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021.
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