P025 Ozanimod Efficacy, Safety, and Histology in Patients with Moderate-to-Severe Ulcerative Colitis During Induction in the Phase 3 True North Study

BACKGROUND: Ozanimod is an oral sphingosine-1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5. Ozanimod has previously demonstrated efficacy and safety in patients with ulcerative colitis (UC) in a phase 2 study (TOUCHSTONE). Here we report data from a 10-week induction period in the phase 3, double-blind, 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 maintenance period are reported separately. METHODS: Adults with moderately-to-severely active UC (total Mayo score 6-12 with a Mayo endoscopy subscore ≥2 and on oral aminosalicylates or corticosteroids) were randomized 2:1 to receive oral ozanimod HCl 1 mg (equivalent to ozanimod 0.92 mg) or placebo once daily during a 10-week randomized induction period. Randomization was stratified by prior tumor necrosis factor inhibitor (TNFi) use and corticosteroid use at screening. The primary endpoint in the induction period was the proportion of patients in clinical remission using the 3-component Mayo score (rectal bleeding score = 0, stool frequency score ≤1 and decrease from baseline ≥1, and endoscopy subscore ≤1) at week 10. Ranked key secondary endpoints were proportions of patients with clinical response (based on 3-component Mayo score), endoscopic improvement (Mayo endoscopic subscore ≤1 without friability), and mucosal healing (endoscopic improvement plus histological remission). Histologic remission was a pre-specified secondary (non-ranked) endpoint. RESULTS: A total of 645 patients were randomized to receive ozanimod (n = 429) or placebo (n = 216); 94% and 89%, respectively, completed the induction period. At week 10, 18.4% and 6.0% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission (difference, 12.4% [95% CI, 7.5-17.2]; P < 0.0001). All key secondary efficacy endpoints showed statistically greater improvements with ozanimod vs placebo. Clinical response was achieved in 47.8% vs 25.9%, endoscopic improvement in 27.3% vs 11.6%, and mucosal healing in 12.6% vs 3.7% for ozanimod vs placebo (all P < 0.001). A significantly greater proportion of patients achieved histologic remission with ozanimod (defined as Geboes <2, 18.2% vs 7.4%; Geboes ≤3.1, 34.7% vs 18.5%; and Geboes ≤1.1, 26.3% vs 11.1% for ozanimod vs placebo, respectively; P < 0.001 for all). In patients with prior TNFi exposure, the proportion of patients achieving clinical remission favored ozanimod but was not significant vs placebo (10.0% vs 4.6%, P = 0.195), while the proportion of patients with clinical response was statistically superior for ozanimod (36.9% vs 18.5%, P = 0.008) at week 10. The most common treatment-emergent adverse events (TEAEs) for patients who received ozanimod vs placebo, respectively, were anemia (4.2% vs 5.6%), nasopharyngitis (3.5% vs 1.4%), and headache (3.3% vs 1.9%). Cardiovascular events were infrequent and included bradycardia (0.5% vs 0%) and hypertension (1.4% vs 0%). Serious TEAEs occurred in 4.0% vs 3.2%, respectively. Serious infections occurred in <1% per group. CONCLUSION: Ozanimod induction for 10 weeks in patients with moderate-to-severe UC resulted in statistically significant improvements in clinical remission, clinical response, endoscopic improvement, mucosal healing, and histologic remission. Ozanimod was well tolerated and no new safety signals were observed.

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