P030 Ozanimod Efficacy, Safety, and Histology in Patients with Moderate-to-Severe Ulcerative Colitis During Maintenance in the Phase 3 True North Study

BACKGROUND: Ozanimod treatment demonstrated efficacy and safety for up to 32 weeks in adults with moderate-to-severe ulcerative colitis (UC) in the phase 2 TOUCHSTONE study. Here, we report week 52 efficacy and safety of ozanimod vs placebo in the maintenance period of the double-blind, phase 3 True North study (NCT02435992). The aim of this study was to evaluate the efficacy and safety of ozanimod in inducing and maintaining remission in patients with moderate-to-severe UC. Results from the 10-week induction period of this study are reported separately). METHODS: Adult patients with clinical response after 10 weeks of ozanimod induction therapy in double-blind and open-label cohorts were eligible for re-randomization 1:1 to double-blind maintenance treatment with ozanimod HCl 1 mg/day (equal to ozanimod 0.92 mg) or matching placebo. Patients were stratified by clinical remission status and corticosteroid use at week 10. Week 52 endpoints were tested sequentially via closed hierarchical procedure. The primary endpoint was proportion of patients in clinical remission per 3-component Mayo score (rectal bleeding score = 0, stool frequency score ≤1 and decrease from baseline ≥1, and endoscopy subscore ≤1). Ranked key secondary endpoints were proportion of patients with a clinical response (based on 3-component Mayo score), endoscopic improvement (Mayo endoscopic subscore ≤1 without friability), maintenance of clinical remission (remission at week 52 for patients who were in remission at week 10), corticosteroid-free remission (remission with no corticosteroids for ≥12 weeks), mucosal healing (endoscopic improvement plus histological remission), and durable clinical remission (remission at weeks 10 and 52 for all patients in maintenance). Histologic remission was a pre-specified secondary (non-ranked) endpoint. RESULTS: A total of 457 patients who responded to ozanimod during induction were re-randomized to double-blind maintenance treatment with either ozanimod (n = 230) or placebo (n = 227), of which, 80.0% and 54.6%, respectively, completed the study. For the primary endpoint, 37.0% and 18.5% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission (difference, 18.6% [95% CI, 10.8-26.4]; P < 0.0001). All key secondary endpoints were statistically significant for ozanimod vs placebo (P < 0.005 for all). In addition, a significantly greater proportion of patients achieved histologic remission with ozanimod (defined as Geboes <2, 33.5% vs 16.3%; Geboes ≤3.1, 49.1% vs 26.4%; Geboes ≤1.1, 42.2% vs 22.5% for ozanimod vs placebo, respectively; P < 0.001 for all). In patients with prior TNFi exposure, the proportions of patients achieving clinical remission (28.9% vs 10.1%) and clinical response (55.3% vs 24.6%) were greater for ozanimod vs placebo (P < 0.001 for both). The most common treatment-emergent adverse events (TEAEs) for patients who received ozanimod vs placebo, respectively, were increases in alanine aminotransferase (4.8% vs 0.4%) and headache (3.5% vs 0.4%). The most common serious TEAE was flare of UC (0.4% vs 4.0%). CONCLUSION: Ozanimod for up to 52 weeks in patients with moderately-to-severely active UC showed benefits on clinical, endoscopic, histologic, and mucosal healing endpoints. Significantly more patients achieved clinical and histologic remission with ozanimod maintenance therapy vs placebo. No new safety signals were observed.

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