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Low discontinuation rates

due to treatment-emergent adverse events that are comparable to placebo1a

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Rates of serious infection were low and comparable to placebo in clinical trials2bc

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Demonstrated safety profile

and long-term safety data observed for over 4 years1-3

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aOverall rates of discontinuation were 6.5% with ZEPOSIA (N=429) vs 11.1% with placebo (N=216) in the induction phase, and 20% with ZEPOSIA (N=230) vs 45.4% with placebo (N=227) in the maintenance phase. Discontinuation rates due to TEAEs in induction were 3.3% for patients taking ZEPOSIA vs 3.2% for patients taking placebo. In maintenance, TEAE discontinuation rates were 1.3% for patients taking ZEPOSIA vs 2.6% for patients taking placebo.1,2

bOverall rates of infection were 9.9% with ZEPOSIA (N=496) vs 10.7% with placebo (N=281) in the induction phase, and 23% with ZEPOSIA (N=230) vs 12% with placebo (N=227) in the maintenance phase. Serious infection rates in the induction phase (UC Study 1 and UC Study 3/TOUCHSTONE) were 0.8% with ZEPOSIA vs 0.4% with placebo. Serious infection rates in the maintenance phase were 0.9% with ZEPOSIA vs 1.8% with placebo.2

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.2

Adverse Reactions With an Incidence of at Least 2% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With UC (Pooled UC Study 1 and Study 3)2
Induction (UC Study 1 and Study 3)d
Adverse Reaction
 ZEPOSIA
0.92 mg
(n=496)gh		 Placebo
(n=281)g
Upper Respiratory Infectione 5% 4%
Liver Test Increasedf 5% 0%
Headache 4% 3%
Pyrexia 3% 2%
Nausea 3% 2%
Arthralgia 3% 1%
Adverse Reactions With an Incidence of at Least 4% in ZEPOSIA-Treated Patients and at Least 1% Greater Than Placebo in Patients With UC (UC Study 2)2
Maintenance
(UC Study 2)
Adverse Reaction
 ZEPOSIA
0.92 mg
(n=230)		 Placebo
(n=227)
Liver Test Increasedi 11% 2%
Headache 5% <1%
  • dAdditional 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.2
  • eIncludes 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.2
  • fIncludes 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, and transaminases increased.2
  • gPercentages were calculated as the sum of each individual study percentage multiplied by its Cochran-Mantel-Haenszel weight.2
  • hZEPOSIA was initiated with a 7-day titration.2
  • iIncludes the following terms: gamma-glutamyl transferase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, hyperbilirubinemia, liver function test increased, and blood alkaline phosphatase increased.2

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 ZEPOSIA in 199 patients with moderately to severely active UC. Participants who completed the induction period and were responders at Week 8 continued to receive the same dose of ZEPOSIA during the maintenance period up to Week 32.4

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

Adverse Events From TRUE NORTH (UC Study 1) Induction Period1
ZEPOSIA 0.92 mg
(n=429)
Placebo
(n=216)
Adverse Event 40.1% 38%
Serious
Adverse Event		 4% 3.2%
Adverse Events From TRUE NORTH (UC Study 2) Maintenance Period1
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.5jk
  • jIn the TRUE NORTH phase 3 studies, 1 case of ischemic stroke (0.2%) was reported in ZEPOSIA-treated patients vs no reports in patients treated with placebo.5
  • kThromboembolic events include pulmonary embolism and venous arterial thrombosis. Major or adverse cardiac events include cardiovascular death, myocardial infarction, and stroke.5

TEAE=treatment-emergent adverse event; 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 weeks2
  • 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 studies2
  • 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 confirmed2

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.2

  • 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 22
  • These values generally returned to greater than 0.2 x 109/L while patients remained on treatment with ZEPOSIA2
  • After discontinuing treatment, the median time for peripheral blood lymphocytes to return to the normal range was approximately 30 days2
    • Approximately 80% to 90% of patients were in the normal range within 3 months2
Pooled Analysis of Controlled and Uncontrolled Trials6
Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit Line Graph Pooled Analysis of Controlled and Uncontrolled Trials: Mean Absolute Lymphocyte Count by Visit Line Graph
  • 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 OLE6
  • Reductions in ALC were observed at Week 5 (the first post-baseline assessment) and sustained through treatment6
  • 60 patients (5.3%) had ALC <0.2 x 109/L at least once during ZEPOSIA treatment6
    • 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 ZEPOSIA6
  • lPatients 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.6

OLE=open-label extension; UC=ulcerative colitis.

Low Discontinuation Rates

Discontinuation Rates Due
to TEAEs That Are Comparable
to Placebo1

Overall Discontinuation Rates1

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)1

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.1,7

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.2

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

Infections and Malignancies

Rates of Serious Infection Were Low and Comparable to Placebo in Clinical Trials2

Rates of Serious Infection in
Clinical Trials2
Inductionm
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 modulator2
  • mAdditional 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.2
Rates of Malignancies in Clinical Trials1
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 ZEPOSIA8
ZEPOSIA 0.92 mg
(n=1158)
PY=1922.5n
Placebo
(n=508)
PY=249.2n
 % (n) IR, per 100 PYo % (n) IR, per 100 PYo
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 trialp (phase 2), 52-week TRUE NORTH trial (phase 3), and the respective OLE trials8
  • Median treatment duration in weeks for ZEPOSIA 0.92 mg and placebo was 65.79 and 17.21, respectively8
  • TEAEs identified in the pooled data from all controlled and uncontrolled UC trials were consistent with the controlled UC trials8
  • nTotal PY 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.8
  • oIncidence rate per 100 PY, 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.8
  • pTOUCHSTONE patients randomized to ZEPOSIA 0.46 mg unapproved dose were only analyzed upon entering TOUCHSTONE OLE and receiving daily ZEPOSIA 0.92 mg.9

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

Long-Term Safety Data Observed Over ~4 Years With ZEPOSIA3,10

This Safety Analysis Includes Patients With UC From the TRUE NORTH Parent Study Who Entered the TRUE NORTH OLE for up to 194 Weeks of ZEPOSIA Exposure10

Estimated Annual Risk = 2.5 per 100 treated patients10

2.5 out of 100 Patients Highlighted Icon 2.5 out of 100 Patients Highlighted Icon

TEAEs Leading
to
Treatment Discontinuation10

2.5

EAIR per
100 PYq

Serious TEAEs10

7.0

EAIR per
100 PYq

Serious Infection10

1.8

EAIR per
100 PYq

Safety From All TRUE NORTH Patients in OLE (N=823)10
Adverse Events
All Patients
in OLE
(N=823)
EAIR per 100 PYq
TEAEs 85.5
Serious TEAEs 7.0
TEAEs Leading to Treatment
Discontinuation		 2.5
Most Frequent TEAEs (Occurring in ≥7% of Patients)
Lymphopeniar 6.1
COVID-19 4.3
Nasopharyngitis 3.8
Anemiar 3.7
Lymphocyte Count Decreasedr 3.7
Alanine Aminotransferase Increasedr 3.2
Arthralgia 3.2
Headache 2.8
Infection (Occurring in ≥3% of Patients)
Serious Infection 1.8
COVID-19 4.3
Nasopharyngitis 3.8
Upper Respiratory Tract Infection 2.4
Herpes Zoster 1.2
Sinusitis 1.2
Bronchitis 1.1
Influenza 1.0
Malignancy (Serious TEAE)
Colon Adenocarcinoma 0.04
Pancreatic Adenocarcinoma 0.04
Basal Cell Carcinoma 0.04
B-Cell Lymphoma 0.04
Follicular Lymphoma, Stage IV 0.04
Malignant Lung Neoplasm 0.04
Prostate Cancer 0.04
Rectal Adenocarcinoma 0.04
Rectal Cancer Stage II 0.04
Cardiovascular Disorders
Hypertension 2.3
Hypertensive Crisis 0.16
Bradycardia 0.12
Third-Degree AV Block 0.04
Myocardial Ischemia 0.12
Ischemic Stroke 0.12
Pulmonary Embolism 0.12
Deep Vein Thrombosis 0.12
Macular Edema 0.12

Three deaths were reported during the OLE: 1 sudden death, 1 due to COVID-19, and 1 due to adenocarcinoma. These deaths were deemed to be unrelated to ZEPOSIA treatment by investigators.3,10

Infection (Occurring in ≥3% of Patients)10

COVID-19:
4.3 EAIR per 100 PYq

Nasopharyngitis:
3.8 EAIR per 100 PYq

Upper Respiratory Tract Infection:
2.4 EAIR per 100 PYq

  • qEAIRs were calculated as numbers of patients/PY × 100.10
  • rLaboratory values were flagged by the central laboratory if they fell outside the standard reference range; investigators decided whether laboratory values qualified as adverse events.11

AV=atrioventricular; EAIR=exposure-adjusted incidence rate; OLE=open-label extension; PY=patient-years; TEAE=treatment-emergent adverse event; UC=ulcerative colitis.

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. Irving P, Long MD, Siegmund B, et al. Efficacy of ozanimod as an induction therapy in advanced therapy-naive ulcerative colitis patients suboptimally controlled on conventional treatments. Oral presentation at: United European Gastroenterology (UEG) Week 2023; Copenhagen, Denmark; October 14–17, 2023. Presentation OP133.
  2. 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.
  3. 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: European Crohn’s and Colitis Organisation (ECCO) Virtual; February 16–19, 2022.
  4. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  5. Data on File. BMS-REF-OZA-0066. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  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. Siegmund B, Irving P, D’Haens G, et al. Ozanimod as a maintenance therapy in advanced therapy-naive ulcerative colitis patients with moderate vs severe endoscopic disease. Oral presentation at: United European Gastroenterology (UEG) Week 2023; Copenhagen, Denmark; October 14–17, 2023. Presentation OP135.
  8. 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.
  9. 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. Presentation DOP37.
  10. 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.
  11. 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.
  12. Data on File. BMS_ZEP008535. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  13. 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.
  14. Danese S, Panaccione R, Abreu MT, et al. Efficacy and safety of approximately 3 years of continuous ozanimod in moderately to severely active ulcerative colitis: interim analysis of the True North open-label extension. J Crohns Colitis. Published online August 31, 2023. doi:10.1093/ecco-jcc/jjad146

References:

  1. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  2. Irving P, Long MD, Siegmund B, et al. Efficacy of ozanimod as an induction therapy in advanced therapy–naive ulcerative colitis patients suboptimally controlled on conventional treatments. Oral presentation at: United European Gastroenterology (UEG) Week 2023; Copenhagen, Denmark; October 14–17, 2023. Presentation OP133.

References:

  1. Efficacy and safety study of ozanimod in ulcerative colitis (Touchstone). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01647516. Updated May 19, 2021. Accessed July 26, 2023.
  2. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  3. Study of ozanimod (RPC1063) in relapsing multiple sclerosis (MS) (SUNBEAM). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02294058. Updated November 25, 2020. Accessed July 26, 2023.
  4. Efficacy and safety study of ozanimod in relapsing multiple sclerosis (RADIANCE). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02047734. Updated February 11, 2021. Accessed July 26, 2023.
  5. Efficacy and safety study of ozanimod (RPC1063) in relapsing multiple sclerosis patients (RADIANCE). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01628393. Updated November 2, 2021. Accessed September 6, 2023.
  6. 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.
  7. Safety and efficacy trial of RPC1063 for moderate to severe ulcerative colitis. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02435992. Updated September 1, 2021. Accessed July 26, 2023.
  8. An extension study of RPC1063 as therapy for moderate to severe ulcerative colitis. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02531126. Updated September 18, 2023. Accessed September 25, 2023.
  9. A multi-site, open-label extension trial of oral RPC1063 in relapsing multiple sclerosis. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02576717. Updated January 30, 2024. Accessed February 6, 2024.
  10. Data on File. BMS-REF-OZA-0039. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  11. Data on File. BMS-REF-OZA-0038. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  12. Selmaj KW, Steinman L, Comi G, et al. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: interim analysis of the DAYBREAK open-label extension study. Poster presented at: 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); Amsterdam, Netherlands; October 26–28, 2022. Poster P334.
  13. Press Release. U.S. Food and Drug Administration approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), a new oral treatment for relapsing forms of multiple sclerosis. Princeton, NJ: Bristol-Myers Squibb Company; 2020.
  14. Press Release. U.S. Food and Drug Administration approves Bristol Myers Squibb’s ZEPOSIA® (ozanimod), an oral treatment for adults with moderately to severely active ulcerative colitis. Princeton, NJ: Bristol-Myers Squibb Company; 2021.
  15. Symphony METYS TRx data and BMS Bridge Dispense data. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  16. 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. Presentation DOP37.

References:

  1. 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.
  2. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  3. 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.
  4. Efficacy and safety study of ozanimod in ulcerative colitis (Touchstone). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT01647516. Updated May 19, 2021. Accessed July 26, 2023.
  5. 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.
  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. 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. Paper presented at: United European Gastroenterology Week Virtual 2020; October 10–14, 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. 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.
  10. Data on File. BMS-REF-OZA-0066. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  11. 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.

References:

  1. Zeposia. Prescribing Information. Bristol-Myers Squibb Company; 2023.
  2. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies [published correction appears in Lancet. 2023 Mar 25;401(10381):1000]. Lancet. 2023;401(10383):1159-1171.
  3. McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions [published correction appears in Lancet. 2021 Sep 25;398(10306):1132]. Lancet. 2021;398(10306):1184-1194.
  4. Roggeri A, Schepers M, Tiane A, et al. Sphingosine-1-phosphate receptor modulators and oligodendroglial cells: beyond immunomodulation. Int J Mol Sci. 2020;21(20):7537.
  5. Pérez-Jeldres T, Tyler CJ, Boyer JD, et al. Cell trafficking interference in inflammatory bowel disease. Inflamm Bowel Dis. 2019;2(25):270-282.
  6. Al-Bawardy B, Shivashankar R, Proctor DD. Novel and emerging therapies for inflammatory bowel disease. Front Pharmacol. 2021;12:651415.
  7. Nikolakis D, de Voogd FAE, Pruijit MJ, et al. The role of the lymphatic system in the pathogenesis and treatment of inflammatory bowel disease. Int J Mol Sci. 2022;23(3):1854.
  8. Harris S, Tran JQ, Southworth H, Spencer CM, Cree BAC, Zamvil SS. Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e839.
  9. 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.
  10. 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.
  11. Kayal M, Shah S. Ulcerative colitis: current and emerging treatment strategies. J Clin Med. 2019;9(1):94.
  12. Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66(2):199-209.
  13. 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(6):669-677.

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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