S1200 Sustained Efficacy and Safety After 5 Years of Continuous Ozanimod Treatment Independent of Clinical Remission Status: An Interim Analysis of the True North Open-Label Extension Study

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Introduction: Ozanimod (OZA) was efficacious and well tolerated over 52 wk in patients (pts) with moderately to severely active ulcerative colitis (UC) in the phase 3 True North (TN) study (NCT02435992). Prior analyses of the ongoing TN open-label extension (OLE; NCT02531126) through OLE Week (W) 142 have demonstrated the efficacy and safety of continuous OZA up to ∼4 y. Methods: The efficacy and safety of OZA were assessed for an additional year in pts who completed OLE W190 (∼5 y of continuous OZA) or discontinued the OLE by data cutoff (January 10, 2024). Pts on continuous OZA throughout TN who achieved clinical response (with or without also achieving clinical remission) at TN W52 and subsequently entered the OLE (referred to as W52 clinical responders) were included in this analysis. Subgroups of W52 clinical responders were also assessed; W52 clinical remitters achieved clinical response and remission and W52 clinical nonremitters achieved clinical response but not remission. Efficacy outcomes were evaluated through OLE W190. Treatment-emergent adverse events (TEAEs) were monitored during TN and the OLE through data cutoff. Results: Of the 131 W52 clinical responders who entered the OLE, 83 (63.4%) were also W52 clinical remitters. Symptomatic responses at OLE W190 were similar in W52 clinical remitters vs nonremitters (97.7% [43/44] vs 100.0% [19/19] in the observed case analysis and 51.8% [43/83] vs 39.6% [19/48] in the nonresponder imputation analysis). Rates of clinical remission, clinical response, endoscopic improvement, and corticosteroid-free remission at OLE W190 were higher in W52 clinical remitters vs nonremitters (Figure 1). Rates of TEAEs, serious TEAEs, TEAEs leading to discontinuation, and TEAEs of interest were generally similar across groups (Table 1). Rates of serious cardiac events were low. No serious hepatic events occurred. Conclusion: Symptomatic, mucosal, and corticosteroid-free clinical outcomes with continuous OZA treatment were sustained up to ∼5 y, with the greatest benefit in pts who achieved clinical remission after 52 wk of OZA treatment. Long-term OZA treatment over ∼5 y continues to be well tolerated with no new safety signals regardless of clinical remission status.Figure 1.: OZA efficacy at OLE W190 in TN W52 clinical responders, remitters, and nonremitters. aRBS = 0, SFS ≤1 (and ≥1-point decrease from baseline SFS), and MES ≤1. b≥2-point and ≥35% decrease from baseline in the 3-component Mayo score (sum of RBS, SFS, and MES) and ≥1-point decrease in RBS or absolute RBS of ≤1. cMES ≤1. dClinical remission while off CS for ≥12 wk. CS, corticosteroid; MES, Mayo endoscopy subscore; NRI, nonresponder imputation; OC, observed case; OLE, open-label extension; OZA, ozanimod; RBS, rectal bleeding subscore; SFS, stool frequency subscore; TN, True North; W, Week. Table 1. - OZA safety During TN and the OLE in TN W52 clinical responders, remitters, and nonremitters Adverse event W52 clinical responders(n=131)a Total PYb = 545.9 W52 clinical remitters(n=83)a Total PYb = 358.9 W52 clinical nonremitters(n=48)a Total PYb = 187.1 n (%) EAIR/100 PYc n (%) EAIR/100 PYc n (%) EAIR/100 PYc TEAEs 116 (88.5) 72.0 71 (85.5) 67.3 45 (93.8) 81.0 Serious TEAEs 28 (21.4) 5.8 17 (20.5) 5.3 11 (22.9) 6.8 TEAEs leading to treatment discontinuation 12 (9.2) 2.2 8 (9.6) 2.2 4 (8.3) 2.2 TEAEs of interest Infection 75 (57.3) 23.3 50 (60.2) 26.8 25 (52.1) 18.4 Serious infection 9 (6.9) 1.7 7 (8.4) 2.1 2 (4.2) 1.1 Herpes zoster 7 (5.3) 1.3 5 (6.0) 1.4 2 (4.2) 1.1 Malignancy Adenocarcinoma pancreas 1 (0.8) 0.2 1 (1.2) 0.3 0 0 Basal cell carcinoma 2 (1.5) 0.4 1 (1.2) 0.3 1 (2.1) 0.5 Lung neoplasm malignant 1 (0.8) 0.2 0 0 1 (2.1) 0.5 Cardiovascular disorders Bradycardia 1 (0.8) 0.2 1 (1.2) 0.3 0 0 Third-degree AV blockd 1 (0.8) 0.2 1 (1.2) 0.3 0 0 Hypertension 17 (13.0) 3.4 13 (15.7) 4.0 4 (8.3) 2.3 Macular edema 1 (0.8) 0.2 1 (1.2) 0.3 0 0 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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