Integrated Long-Term Safety of Ozanimod Across Two Different Indications: Results from Clinical Trials in Patients With Moderately to Severely Active Ulcerative Colitis or Relapsing Multiple Sclerosis

Background:
Ozanimod is a selective sphingosine 1-phosphate (S1P) receptor 1 and 5 modulator approved for the treatment of moderately to severely active ulcerative colitis (UC) or relapsing multiple sclerosis (RMS). A prior analysis of clinical trial data showed that long-term treatment with ozanimod was well tolerated across 2,715 patient-years (PY) of exposure in patients with UC and 11,732 PY of exposure in patients with RMS. This analysis provides a pooled safety evaluation of ozanimod in patients with moderately to severely active UC or RMS with additional ozanimod exposure.
Methods:
Pooled data in patients with UC who received ozanimod in phase 2 (NCT01647516), phase 3 (NCT02435592), and respective open-label extension (OLE; NCT02531126) trials were examined from December 2, 2015, through November 17, 2023. Data in patients with RMS who received ozanimod in an OLE trial (NCT02576717) after enrolling from phase 1–3 trials were examined from October 16, 2015, through April 7, 2023. Outcomes included treatment-emergent adverse events (TEAEs) and laboratory abnormalities.
Results:
Total ozanimod exposure was 3479 PY in 1158 patients with UC and 12,663 PY in 2494 patients with RMS (16,142 PY in 3652 patients combined). In UC and RMS patients, 59.4% and 33.1% were male (41.5% combined), mean age was 41.6 years and 36.1 years (37.8 years combined), and mean body mass index was 25.4 kg/m² and 24.3 kg/m² (24.7 kg/m² combined) at baseline. Exposure-adjusted incidence rates (EAIRs) per 100 PY in the UC and RMS populations were 81.1 and 65.0 for TEAEs (68.9 combined), 7.0 and 3.2 for serious TEAEs (4.0 combined), and 3.5 and 0.8 for TEAEs leading to treatment discontinuation (1.4 combined). EAIRs of most TEAEs of interest (ie, herpes zoster, serious infection, malignancy, hypertension, bradycardia, complete atrioventricular block, myocardial ischemia, ischemic stroke, pulmonary embolism, deep vein thrombosis, macular edema, and drug-induced liver injury) were low and similar across populations. The most common TEAEs as reported by investigators were lymphopenia (13.0%, EAIR 4.9/100 PY) and COVID-19 (10.2%, EAIR 3.6/100 PY) in patients with UC and nasopharyngitis (21.3%, EAIR 5.0/100 PY) and headache (17.1%, EAIR 3.8/100 PY) in patients with RMS. Absolute lymphocyte count < 200 cells/µl occurred in 6.8% of patients with UC and 14.8% of patients with RMS during OLE trials but were not temporally associated with serious or opportunistic infections. Most liver enzyme elevations during OLE trials were transient and resolved without treatment interruption; no serious hepatic events or Hy’s law cases occurred. There were 5 deaths (0.4%) in UC patients and 15 deaths (0.6%) in RMS patients.
Conclusions:
These data confirm the established safety profile of ozanimod, a once-daily oral S1P receptor 1 and 5 modulator, over the long-term, with >16,000 PYs of exposure in moderately to severely active UC or RMS.