The Food and Drug Administration (FDA) has approved Zeposia® (ozanimod) for the treatment of moderately to severely active ulcerative colitis in adults.
The approval was based on data from the double-blind, placebo-controlled phase 3 True North trial (ClinicalTrials.gov Identifier: NCT02435992) that assessed the efficacy and safety of ozanimod, a sphingosine 1-phosphate receptor modulator, 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 ozanimod 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 ozanimod 0.92mg (n=230) or placebo (n=227) for a total of 52 weeks of treatment.
Results showed that ozanimod 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, ozanimod 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 ozanimod-treated patients vs 17% of patients who received placebo.
As for safety, the most common adverse reactions reported in the ulcerative colitis trials included increased liver tests, upper respiratory infection, and headache. Ozanimod is contraindicated in patients who in the last 6 months, have experienced a myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; have the presence of Mobitz type II second degree or third degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker; have severe untreated sleep apnea; or are taking a monoamine oxidase inhibitor.
Before initiating therapy, a complete blood count (with lymphocyte count), an electrocardiogram, and liver function tests should be obtained. For patients with a history of uveitis or macular edema, an ophthalmic assessment is required.
Zeposia is supplied in 0.23mg, 0.46mg, 0.92mg strength capsules.
- US Food and Drug Administration approves Bristol Myers Squibb’s Zeposia® (ozanimod), an oral treatment for adults with moderately to severely active ulcerative colitis. [press release]. Princeton, NJ: Bristol Myers Squibb. May 27, 2021.
- Zeposia [package insert]. Princeton, NJ: Bristol Myers Squibb. 2021.