S1476 Safety of Long-Term Ozanimod Treatment Up to 5 Years in Patients With Moderately to Severely Active Ulcerative Colitis: An Interim Analysis of the True North Open-Label Extension

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Introduction: The 52-week, phase 3 True North (TN) study (NCT02435992) demonstrated the efficacy and safety of ozanimod (OZA), a highly selective sphingosine 1-phosphate receptor 1 and 5 modulator, in patients (pts) with moderately to severely active ulcerative colitis (UC). A prior analysis reported the long-term safety of OZA up to ∼4 y from TN baseline through week (W) 142 of the ongoing TN open-label extension (OLE; NCT02531126). Methods: This analysis assessed the cumulative long-term safety of OZA with an additional year of exposure (pt disposition available until OLE W190 [up to ∼5 y of OZA]). All pts who entered the OLE from TN (ie, clinical nonresponders at W10 and those who lost response during maintenance or completed maintenance at W52) were included in this analysis. Treatment-emergent adverse events (TEAEs) were monitored from the first dose of OZA in TN or the OLE through data cutoff; exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) are presented. Lab abnormalities, including absolute lymphocyte count (ALC) reductions, were assessed during the OLE through data cutoff. Results: A total of 823 pts entered the TN OLE. At data cutoff, 43.0% of pts had completed OLE W190 and total OZA exposure was 2681 PY. Overall, the cumulative safety assessments did not meaningfully change with an additional year of OZA exposure (Table 1). EAIRs of TEAEs, serious TEAEs, and TEAEs leading to treatment discontinuation remained consistent, and there were no new cases of malignancy, bradycardia, third-degree atrioventricular (AV) block, myocardial ischemia, ischemic stroke, pulmonary embolism, deep vein thrombosis, or macular edema with an additional year of OZA exposure. Three pts newly developed infections; however, only 1 pt had a serious infection (keratouveitis), which was not related to treatment. Two additional pts experienced mild hypertension. Reductions in ALC < 500 cells/µl were common in the OLE (57.2%), but few pts had ALC < 200 cells/µl (6.6%). Occurrence of ALC < 200 cells/µl was not temporally associated with serious or opportunistic infections. Most alanine aminotransferase and aspartate aminotransferase elevations were transient and resolved without treatment interruption, and no serious hepatic events occurred. Conclusion: The ongoing safety profile of OZA is consistent with previous analyses, with no new safety concerns identified. Long-term OZA use representing 2681 PY of exposure continues to be well tolerated in pts with moderately to severely active UC. Table 1. - OZA safety during TN and the OLE in TN W52 clinical responders, remitters, and nonremitters Adverse event Up to ∼4 y of OZA exposurea (n=823)Total PYc = 2536 Up to ∼5 y of OZA exposureb (n=823)Total PYc = 2681 n (%) EAIRd n (%)e EAIRd TEAEs 685 (83.2) 85.5 687 (83.5) 85.1 Serious TEAEs 158 (19.2) 7.0 163 (19.8)f 6.8 TEAEs leading to treatment discontinuation 64 (7.8) 2.5 66 (8.0) 2.5 Infection 378 (45.9) 22.7 381 (46.3) 22.1 Herpes zoster 30 (3.6) 1.2 31 (3.8) 1.2 COVID-19 103 (12.5) 4.3 103 (12.5) 4.1 Serious infection 44 (5.3) 1.8 45 (5.5) 1.7 Malignancy 18 (2.2) 0.71 17 (2.1) 0.63 Bradycardia 3 (0.4) 0.12 3 (0.4) 0.11 Third-degree AV block 1 (0.1) 0.04 1 (0.1) 0.04 Hypertension 55 (6.7) 2.3 56 (6.8) 2.2 Myocardial ischemia 3 (0.4) 0.12 3 (0.4) 0.11 Ischemic stroke 3 (0.4) 0.12 3 (0.4) 0.11 Pulmonary embolism 3 (0.4) 0.12 3 (0.4) 0.11 Deep vein thrombosis 3 (0.4) 0.12 3 (0.4) 0.11 Macular edema 3 (0.4) 0.12 3 (0.4) 0.11 Cystoid macular edema 3 (0.4) 0.12 3 (0.4) 0.11 aData were collected from the beginning of TN through the OLE data cutoff for this analysis (January 10, 2024 ). bTotal PY was calculated as the sum of the number of years on study contributed by each pt from time of first dose to last date on study . cEAIRs were calculated as number of pts/PY × 100 . dOccurred in a 75-year-old pt with elevated body mass index and a history of long-standing hypertension, did not require OZA disruption, and was attributed to atherosclerotic disease affecting cardiac conduction . AV, atrioventricular; EAIR, exposure-adjusted incidence rate; OLE, open-label extension; OZA, ozanimod; Pt, patient; PY, patient-years; TEAE, treatment-emergent adverse event; TN, True North; W, Week.

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