P035 Ozanimod for Moderate-to-Severe Ulcerative Colitis: North American Population Results During Induction and Maintenance in the Phase 3 True North Study.

Background: True North is a phase 3, randomized, double-blind, placebo-controlled trial conducted at 285 sites in 30 countries (NCT02435992). Treatment with once-daily ozanimod (an oral sphingosine 1-phosphate [S1P] receptor modulator selectively targeting S1P1 and S1P5) in patients with moderately-to-severely active ulcerative colitis (UC) showed significant improvements in primary and all key secondary endpoints. Here we report findings on the consistency of clinical and endoscopic endpoints in the global and North American population.

Methods: In True North, patients received either double-blind treatment with ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or matching placebo, or open-label ozanimod 0.92 mg over a 10-week induction period. Patients with clinical response to ozanimod at Week 10 were re-randomized 1:1 to receive double-blind maintenance treatment with ozanimod 0.92 mg or placebo through Week 52. The primary endpoint was proportion of patients in clinical remission at Weeks 10 and 52; key secondary endpoints included clinical response and endoscopic improvement. The global population included 1012 patients who received at least 1 dose of study medication during induction, and 457 who received at least 1 dose of study medication during maintenance. Here, we examine the results from the patients in the North American sites.

Results: A total of 247 patients were enrolled in North America, of which 167 received double-blind ozanimod (n=107) or placebo (n=60) during induction. At baseline, 41.1% and 48.3% of patients in the ozanimod and placebo groups, respectively, had previously received a biologic treatment for UC. At Week 10, 15.9% and 3.3% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 46.7% and 15.0% achieved clinical response and 26.2% and 10.0% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. In patients with prior exposure to tumor necrosis factor inhibitor (TNFi), the proportion with clinical response favored ozanimod (35.7%) vs placebo (11.5%), while the proportion with clinical remission and endoscopic improvement did not favor ozanimod. In patients with no prior TNFi exposure, greater responses were seen with ozanimod vs placebo for all 3 endpoints. During maintenance, 105 patients from North America were re-randomized to treatment with ozanimod (n=56) or placebo (n=49). At Week 52, 39.3% and 12.2% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 58.9% and 26.5% achieved clinical response and 50.0% and 16.3% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. The proportion of patients with clinical remission, clinical response, and endoscopic improvement favored ozanimod vs placebo regardless of prior TNFi use. These outcomes from the North American population are generally consistent with those previously reported from the global population.

Conclusion: In this post-hoc analysis, consistent with the global population, ozanimod treatment for up to 52 weeks in North American patients with moderately-to-severely active UC showed benefits on clinical and endoscopic endpoints.