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Select Endpoints From TRUE NORTH

The primary endpoint was clinical remission at Weeks 10 and 52. Key secondary endpoints included clinical response, endoscopic improvement, endoscopic-histologic mucosal improvement (EHMI) at Weeks 10 and 52, and CS-free clinical remission at Week 52.1 For full study design, click here.

TRUE NORTH Induction Data

Week 10

Post-hoc Analysis:
Symptomatic Response

Clinical
Response

Clinical
Remission

Endoscopic
Improvement

EHMI

Post-hoc Analysis:
Symptomatic Response

Clinical Response

Clinical Remission

Endoscopic Improvement

EHMI

POST-HOC ANALYSIS: SYMPTOMATIC RESPONSEa OBSERVED IN PATIENTS TREATED WITH ZEPOSIA AS EARLY AS WEEK 2—1 WEEK AFTER COMPLETING THE 7-DAY DOSE TITRATION1-5

Patients in Symptomatic Response (%) at 10 Weeks Patients in Symptomatic Response (%) at 10 Weeks

In a post-hoc analysis, patients treated with ZEPOSIA observed a decrease in RBS and SFS as early as Week 2, 1 week after completing the 7-day dose titration.1,3

  • Efficacy analyses in the moderate, biologic-naïve subgroup were not prespecified.4
  • aSymptomatic clinical response is defined as a decrease from baseline in the combined 6-point SFS + RBS by ≥1 point and >30%, and a decrease of ≥1 point in RBS or an absolute RBS of ≤1 point.2,5
  • bData are based on the nonresponder imputation.2
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

RAPID CLINICAL RESPONSE WAS OBSERVED AT WEEK
10 IN THE ALL-PATIENTS GROUP1a

Clinical Response (Key Secondary Endpoint) at Week 10 Graph Clinical Response (Key Secondary Endpoint) at Week 10 Graph
  • aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1.1,4
  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

Post-hoc analysis:
49% of nonrespondersd who entered the open-label extension at Week 10 after the
induction period observed symptomatic clinical response by Week 20e (open-label extension
Week 10)6

  • Symptomatic clinical response is defined as a reduction from baseline in the partial Mayo score of ≥1 point and ≥30% and a ≥1-point decrease in RBS or absolute RBS ≤1.2,5
  • Efficacy analyses of symptomatic response were not prespecified.
  • dNonresponders were patients who did not achieve clinical response (defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1) on ZEPOSIA at Week 10 of induction and entered the OLE.1,6
  • eData are based on the nonresponder imputation.6

EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

CLINICAL REMISSION WAS OBSERVED AT WEEK 10
IN THE ALL-PATIENTS GROUP1a

Clinical Remission (Primary Endpoint) Graph at Week 10 Clinical Remission (Primary Endpoint) Graph at Week 10
  • aClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability.1,4
  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

ENDOSCOPIC IMPROVEMENT OBSERVED AT
WEEK 101a

Endoscopic Improvement at Week 10 Graph Endoscopic Improvement at Week 10 Graph
  • aEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.1,4
  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

ZEPOSIA DEMONSTRATED MUCOSAL HEALING DEFINED BY SIGNIFICANT
ENDOSCOPIC-HISTOLOGIC MUCOSAL IMPROVEMENT AT WEEK 101a

Endoscopic-Histologic Mucosal Improvement at Week 10 Graph Endoscopic-Histologic Mucosal Improvement at Week 10 Graph
  • The relationship of EHMI, as defined in UC Study 1 at Week 10, to disease progression and long-term outcomes, was not evaluated.1
  • aEndoscopic-histologic mucosal improvement is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0).1,4
  • bTreatment difference (adjusted for stratification factors of prior TNFi exposure and corticosteroid use at baseline).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

TRUE NORTH Maintenance Data

Week 52

Clinical
Response

Clinical
Remission

CS-Free
Remission

Endoscopic
Improvement

EHMI

Clinical Response

Clinical Remission

CS-Free Remission

Endoscopic Improvement

EHMI

CLINICAL RESPONSE INCREASED AT WEEK 52 IN THE ALL-PATIENTS GROUP1a

Rapid Clinical Response at 52 Weeks Graph Rapid Clinical Response at 52 Weeks Graph
  • aClinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 1.1,4
  • bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

CLINICAL REMISSION WAS SUSTAINED AT WEEK 52 IN THE ALL-PATIENTS GROUP1a

Clinical Remission (Primary Endpoint) Graph at Week 52 Clinical Remission (Primary Endpoint) Graph at Week 52
  • aClinical remission is defined as RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability.1,4
  • bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

CS-FREE REMISSION OBSERVED AT WEEK 52 IN THE ALL-PATIENTS GROUP1a

CS-Free Remission Observed at Week 52 Graph CS-Free Remission Observed at Week 52 Graph
  • aCS-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥12 weeks.1,4
  • bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

ENDOSCOPIC IMPROVEMENT OBSERVED AT
WEEK 521a

Endoscopic Improvement at Week 52 Graph Endoscopic Improvement at Week 52 Graph
  • aEndoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.1
  • bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

ZEPOSIA DEMONSTRATED MUCOSAL HEALING DEFINED BY SIGNIFICANT ENDOSCOPIC-HISTOLOGIC MUCOSAL IMPROVEMENT AT WEEK 521a

Endoscopic-Histologic Mucosal Improvement at Week 52 Graph Endoscopic-Histologic Mucosal Improvement at Week 52 Graph
  • The relationship of EHMI, as defined in UC Study 2 at Week 52, to disease progression and long-term outcomes, was not evaluated.1
  • aEndoscopic-histologic mucosal improvement is defined as both a Mayo endoscopy subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, ie, Geboes <2.0).1,4
  • bTreatment difference (adjusted for stratification factors of clinical remission and concomitant corticosteroid use at Week 10).1
  • cModerate biologic-naïve subgroup included patients with a Mayo endoscopy subscore of 2.4

EHMI=endoscopic-histologic mucosal improvement; RBS=rectal bleeding subscore; SFS=stool frequency subscore; TNFi=tumor necrosis factor inhibitor; UC=ulcerative colitis.

TRUE NORTH Open-Label Extension Data, Up to 3 Years

Week 98
(Week 46 of OLE)

Week 146
(Week 94 of OLE)

Week 98 (Week 46 of OLE)

Week 146 (Week 94 of OLE)

LONG-TERM RESPONSE, REMISSION, AND CS-FREE REMISSION DATA AT
WEEK 98 (WEEK 46 OF OLE) OF ZEPOSIA, INTERIM EFFICACY ANALYSIS7,8

Long-term Response, Remission, and CS-Free Remission Graph at Week 98 Long-term Response, Remission, and CS-Free Remission Graph at Week 98
  • aSubset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure (observed case analysis).7
  • bSubset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure (observed case analysis).8
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9
  • In the NRI analysis of a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure, 71% (n=93/131) were in clinical response at Week 98 (Week 46 of OLE) and 56% (n=74/131) were in clinical response at Week 146 (Week 94 of OLE).7
  • In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 65% (n=54/83) were in clinical remission at Week 98 (Week 46 of OLE) and 49% (n=41/83) were in clinical remission at Week 146 (Week 94 of OLE).8,9
  • In the NRI analysis of patients who were in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 64% (n=53/83) were in CS-free remission at Week 98 (Week 46 of the OLE) and 48% (n=40/83) were in CS-free remission at Week 146 (Week 94 of the OLE).8
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9
  • Clinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 11,8
  • Clinical remission is defined as: RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability1,8
  • CS-free remission is defined as clinical remission while off corticosteroids for ≥12 weeks1,8
  • OLE Study Design
  • The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE as of the cutoff date (January 10, 2022).7,10,11 For full study design, click here.
  • OLE endpoints were evaluated at Week 46 and Week 94 for a subset of patients who were in clinical remission or clinical response at Week 52 of the TRUE NORTH parent study and who had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study. Mean ZEPOSIA exposure through the OLE was 2.7 years.7,9,10,12,13
  • Data were analyzed in the intent-to-treat population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.9,10
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9,10

CS=corticosteroid; NRI=nonresponder imputation; OC=observed cases; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; UC=ulcerative colitis.

LONG-TERM RESPONSE, REMISSION, AND CS-FREE REMISSION DATA AT
WEEK 146 (WEEK 94 OF OLE) OF ZEPOSIA, INTERIM EFFICACY ANALYSIS7,8

Long-term Response, Remission, and CS-Free Remission Graph at Week 146 Long-term Response, Remission, and CS-Free Remission Graph at Week 146
  • aSubset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure (observed case analysis).7
  • bSubset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure (observed case analysis).8
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9
  • In the NRI analysis of a subset of patients in clinical response at Week 52 and had continuous ZEPOSIA exposure, 71% (n=93/131) were in clinical response at Week 98 (Week 46 of OLE) and 56% (n=74/131) were in clinical response at Week 146 (Week 94 of OLE).7
  • In the NRI analysis of a subset of patients in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 65% (n=54/83) were in clinical remission at Week 98 (Week 46 of OLE) and 49% (n=41/83) were in clinical remission at Week 146 (Week 94 of OLE).8,9
  • In the NRI analysis of patients who were in clinical remission at Week 52 and had continuous ZEPOSIA exposure, 64% (n=53/83) were in CS-free remission at Week 98 (Week 46 of the OLE) and 48% (n=40/83) were in CS-free remission at Week 146 (Week 94 of the OLE).8
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9
  • Clinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS of 0 or 11,8
  • Clinical remission is defined as: RBS=0, SFS=0 or 1 (and a decrease of ≥1 point from baseline SFS), and endoscopy subscore=0 or 1 without friability1,8
  • CS-free remission is defined as clinical remission while off corticosteroids for ≥12 weeks1,8
  • OLE Study Design
  • The TRUE NORTH OLE is an ongoing trial that enrolled participants who were nonresponders at the end of induction, experienced disease relapse during maintenance, or completed maintenance treatment in the phase 3 TRUE NORTH study or remained at study closure and received once-daily oral ZEPOSIA 0.92 mg in the phase 2 TOUCHSTONE OLE. A total of 823 patients from TRUE NORTH entered the TRUE NORTH OLE as of the cutoff date (January 10, 2022).7,10,11 For full study design, click here.
  • OLE endpoints were evaluated at Week 46 and Week 94 for a subset of patients who were in clinical remission or clinical response at Week 52 of the TRUE NORTH parent study and who had continuous ZEPOSIA exposure. Endpoints include clinical remission, clinical response, endoscopic improvement, and CS-free remission. Safety was evaluated for all 823 patients who entered the OLE from the TRUE NORTH parent study. Mean ZEPOSIA exposure through the OLE was 2.7 years.7,9,10,12,13
  • Data were analyzed in the intent-to-treat population using OC and NRI. OC used the number of patients remaining in the study at the corresponding time point. NRI used the number of patients remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed.9,10
  • These analyses were not prespecified and represent a subgroup of all patients from TRUE NORTH who entered the OLE.9,10

CS=corticosteroid; NRI=nonresponder imputation; OC=observed cases; OLE=open-label extension; RBS=rectal bleeding subscore; SFS=stool frequency subscore; UC=ulcerative colitis.

Understand the Study
Design

Review the
Demonstrated
Safety Profile1

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.

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  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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  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.
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  10. Data on File. BMS-REF-OZA-0039. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
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  12. 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.
  13. Selmaj K, 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.
  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.
  15. 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.
  16. Danese S, Feagan BG, Wolf DC, et al. Ozanimod as maintenance therapy in patients with moderate-to-severe ulcerative colitis: results from the phase 3, randomized, double-blind, placebo-controlled True North study. Presented at: United European Gastroenterology (UEG) Week; Virtual, October 11-13, 2020. Presentation LB10.
  17. 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.
  18. 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.
  19. Data on File. BMS-REF-OZA-0031. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  20. 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.
  21. 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.

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  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.
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  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.
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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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