Colorectal disorders:
Indications for: ZEPOSIA
Moderately to severely active ulcerative colitis (UC) in adults.
Clinical Trials:
The approval was based on data from the double-blind, placebo-controlled phase 3 True North trial that assessed the efficacy and safety of Zeposia as an induction and maintenance therapy for adults with moderately to severely active ulcerative colitis who had an inadequate response to prior treatment.
In the induction phase, patients were randomly assigned to receive either Zeposia 0.92mg orally once daily (n=429) or placebo (n=216) for 10 weeks. Patients who achieved a clinical response in the induction phase or who were part of an open-label arm were eligible to proceed into the maintenance phase in which they were randomly assigned to receive Zeposia 0.92mg (n=230) or placebo (n=227) for a total of 52 weeks of treatment.
Results showed that Zeposia met the primary endpoints in both phases, achieving statistically significant clinical remission at week 10 in the induction phase (18% vs 6% for placebo; treatment difference: 12% [95% CI, 8-17]; P<.0001) and at week 52 in the maintenance phase (37% vs 19% for placebo; treatment difference: 19% [95% CI, 11-26]; P<.0001).
Additionally, Zeposia treatment led to improvements in clinical response, endoscopic improvement, and endoscopic-histologic mucosal healing compared with placebo at week 10 and at week 52 (secondary endpoints). In the maintenance period, corticosteroid-free clinical remission was observed in 32% of Zeposia-treated patients vs 17% of patients who received placebo.
Adult Dosage:
Swallow whole. Initiate dose titration regimen (Days 1–4): 0.23mg once daily; (Days 5–7): 0.46mg once daily. Maintenance (starting Day 8): 0.92mg once daily. Re-initiation after dose interruption (during 1st 2 weeks): start with Day 1 of titration regimen; (after the 1st 2 weeks): continue treatment as planned. Mild or moderate hepatic impairment: 0.92mg once every other day starting on Day 8 after initial titration.
Children Dosage:
Not established.
ZEPOSIA Contraindications:
Recent (within last 6 months) occurrence of: MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure. Presence of Mobitz Type II 2nd- or 3rd-degree AV block, sick sinus syndrome, or sino-atrial block, unless paced. Severe untreated sleep apnea. Concomitant MAOIs during and within 14 days (eg, selegiline, phenelzine, linezolid).
ZEPOSIA Warnings/Precautions:
Increased risk of infections (may be fatal). Obtain recent CBC (within last 6 months or after discontinuation of prior MS or UC therapy) prior to initiation. Monitor for infections during and for up to 3 months after discontinuation. Consider treatment interruption if serious infection develops. Active infection: do not start until infection resolved. Test for antibodies to varicella zoster virus prior to initiation; if negative, consider immunization before starting ozanimod. Withhold and evaluate at first sign/symptom of progressive multifocal leukoencephalopathy (PML); discontinue if confirmed and monitor for immune reconstitution inflammatory syndrome (IRIS). Immunosuppressed. Risk of bradyarrhythmia, AV conduction delays: titration is required for treatment initiation. Obtain ECG prior to initiation to determine if preexisting conduction abnormalities are present. Significant QT prolongation, arrhythmias, ischemic heart disease, HF, history of cardiac arrest or MI, cerebrovascular disease, uncontrolled hypertension: refer to cardiologist if treatment is considered. Monitor BP during treatment. Obtain recent LFTs (within 6 months) prior to initiation. Monitor for hepatic dysfunction; discontinue if significant liver injury is confirmed. History of severe liver disease. Respiratory function: perform spirometric evaluation as needed. Diabetes, history of uveitis: increased risk of macular edema. Do ophthalmic exam at baseline, and if any change in vision during therapy. MS: monitor for severe increase in disability after treatment discontinuation. Severe hepatic impairment: not recommended. Elderly. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 3 months after discontinuation. Nursing mothers.
ZEPOSIA Classification:
Sphingosine 1-phosphate receptor modulator.
ZEPOSIA Interactions:
See Contraindications. Concomitant antineoplastic, immunosuppressant or immune-modulating therapies may increase risk of immunosuppression; use caution when switching from long-acting immunotherapies or initiating other drugs 4 weeks after discontinuing ozanimod. Initiation after treatment with alemtuzumab: not recommended. Concomitant QT prolonging drugs (eg, quinidine, procainamide, amiodarone, sotalol): risk of torsades de pointes (in bradycardia). Avoid live attenuated vaccines during and for up to 3 months after discontinuing ozanimod; may have suboptimal response; if live vaccines are required, administer at least 1 month prior to initiating ozanimod. Potentiated by strong CYP2C8 (eg, gemfibrozil); avoid concomitant use. Antagonized by strong CYP2C8 inducers (eg, rifampin); avoid concomitant use. Concomitant drugs or OTC meds that increase norepinephrine or serotonin (eg, opioids, SSRIs, SNRIs, tricyclics, tyramine): not recommended. Potential additive effects on HR when concomitant with both a beta blocker and a calcium channel blocker (eg, verapamil, diltiazem); do not initiate ozanimod, if necessary, refer to cardiologist. Avoid high amounts (>150mg) of tyramine-containing food (eg, aged cheese, pickled herring).
Adverse Reactions:
Upper respiratory infection, hepatic transaminase elevation, headache; also for MS: orthostatic hypotension, urinary tract infection, back pain, hypertension; transient reduction in HR, malignancies, macular edema, respiratory effects, PML, IRIS; rare: posterior reversible encephalopathy syndrome (discontinue if suspected).
Drug Elimination:
Fecal (37%), renal (26%). Half-life: ~21 hours.
Generic Drug Availability:
NO
How Supplied:
Caps 0.92mg—30; 7-Day Starter Pack—7 (4 × 0.23mg + 3 × 0.46mg); Starter Pack—37 (7-cap starter pack + 30 × 0.92mg)
Multiple sclerosis:
Indications for: ZEPOSIA
Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Clinical Trials:
The approval was based on data from 2 double-blind, parallel-group, active comparator-controlled clinical trials in patients with relapsing forms of MS. Both studies included patients who had experienced at least 1 relapse within the prior year, or 1 relapse within the prior 2 years with evidence of at least a gadolinium-enhancing (GdE) lesion in the prior year, and had an Expanded Disability Status Scale score from 0 to 5.0 at baseline.
Patients were randomly assigned to receive Zeposia 0.92mg given orally once daily, beginning with a dose titration, or interferon beta-1a 30mcg given intramuscularly once weekly. The primary end point of both studies was annualized relapse rate (ARR) over the treatment period.
Results showed that in both trials, the ARR was statistically significantly lower in patients treated with Zeposia than in patients who received interferon beta-1a (Study 1: ARR 0.181 vs 0.350, respectively; Study 2: ARR 0.172 vs 0.276, respectively). Compared with interferon beta-1a, Zeposia demonstrated a relative reduction in ARR of 48% (P<.0001) through 1 year (Study 1) and 38% (P <.0001) at 2 years (Study 2). A similar effect was observed in exploratory subgroups defined by sex, age, prior nonsteroid therapy for MS, and baseline disease activity.
Moreover, the number of new or enlarging T2 hyperintense lesions and the number of GdE lesions were found to be statistically significantly lower in ozanimod-treated patients compared with patients who received interferon beta-1a.
Adult Dosage:
Swallow whole. Initiate dose titration regimen (Days 1–4): 0.23mg once daily; (Days 5–7): 0.46mg once daily. Maintenance (starting Day 8): 0.92mg once daily. Re-initiation after dose interruption (during 1st 2 weeks): start with Day 1 of titration regimen; (after the 1st 2 weeks): continue treatment as planned. Mild or moderate hepatic impairment: 0.92mg once every other day starting on Day 8 after initial titration.
Children Dosage:
Not established.
ZEPOSIA Contraindications:
Recent (within last 6 months) occurrence of: MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure. Presence of Mobitz Type II 2nd- or 3rd-degree AV block, sick sinus syndrome, or sino-atrial block, unless paced. Severe untreated sleep apnea. Concomitant MAOIs during and within 14 days (eg, selegiline, phenelzine, linezolid).
ZEPOSIA Warnings/Precautions:
Increased risk of infections (may be fatal). Obtain recent CBC (within last 6 months or after discontinuation of prior MS or UC therapy) prior to initiation. Monitor for infections during and for up to 3 months after discontinuation. Consider treatment interruption if serious infection develops. Active infection: do not start until infection resolved. Test for antibodies to varicella zoster virus prior to initiation; if negative, consider immunization before starting ozanimod. Withhold and evaluate at first sign/symptom of progressive multifocal leukoencephalopathy (PML); discontinue if confirmed and monitor for immune reconstitution inflammatory syndrome (IRIS). Immunosuppressed. Risk of bradyarrhythmia, AV conduction delays: titration is required for treatment initiation. Obtain ECG prior to initiation to determine if preexisting conduction abnormalities are present. Significant QT prolongation, arrhythmias, ischemic heart disease, HF, history of cardiac arrest or MI, cerebrovascular disease, uncontrolled hypertension: refer to cardiologist if treatment is considered. Monitor BP during treatment. Obtain recent LFTs (within 6 months) prior to initiation. Monitor for hepatic dysfunction; discontinue if significant liver injury is confirmed. History of severe liver disease. Respiratory function: perform spirometric evaluation as needed. Diabetes, history of uveitis: increased risk of macular edema. Do ophthalmic exam at baseline, and if any change in vision during therapy. MS: monitor for severe increase in disability after treatment discontinuation. Severe hepatic impairment: not recommended. Elderly. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 3 months after discontinuation. Nursing mothers.
ZEPOSIA Classification:
Sphingosine 1-phosphate receptor modulator.
ZEPOSIA Interactions:
See Contraindications. Concomitant antineoplastic, immunosuppressant or immune-modulating therapies may increase risk of immunosuppression; use caution when switching from long-acting immunotherapies or initiating other drugs 4 weeks after discontinuing ozanimod. Initiation after treatment with alemtuzumab: not recommended. Concomitant QT prolonging drugs (eg, quinidine, procainamide, amiodarone, sotalol): risk of torsades de pointes (in bradycardia). Avoid live attenuated vaccines during and for up to 3 months after discontinuing ozanimod; may have suboptimal response; if live vaccines are required, administer at least 1 month prior to initiating ozanimod. Potentiated by strong CYP2C8 (eg, gemfibrozil); avoid concomitant use. Antagonized by strong CYP2C8 inducers (eg, rifampin); avoid concomitant use. Concomitant drugs or OTC meds that increase norepinephrine or serotonin (eg, opioids, SSRIs, SNRIs, tricyclics, tyramine): not recommended. Potential additive effects on HR when concomitant with both a beta blocker and a calcium channel blocker (eg, verapamil, diltiazem); do not initiate ozanimod, if necessary, refer to cardiologist. Avoid high amounts (>150mg) of tyramine-containing food (eg, aged cheese, pickled herring).
Adverse Reactions:
Upper respiratory infection, hepatic transaminase elevation, headache; also for MS: orthostatic hypotension, urinary tract infection, back pain, hypertension; transient reduction in HR, malignancies, macular edema, respiratory effects, PML, IRIS; rare: posterior reversible encephalopathy syndrome (discontinue if suspected).
Drug Elimination:
Fecal (37%), renal (26%). Half-life: ~21 hours.
Generic Drug Availability:
NO
How Supplied:
Caps 0.92mg—30; 7-Day Starter Pack—7 (4 × 0.23mg + 3 × 0.46mg); Starter Pack—37 (7-cap starter pack + 30 × 0.92mg)
