P031 Ozanimod in Patients with Moderate-to-Severe Ulcerative Colitis: Long-Term Safety and Efficacy from the Phase 2 TOUCHSTONE Study 4-Year Open-Label Extension

BACKGROUND: Ozanimod is a potent, selective, sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator that has demonstrated safety and efficacy in patients with moderate-to-severe ulcerative colitis (UC) in the randomized, placebo-controlled, phase 2 TOUCHSTONE study (NCT01647516). This analysis presents data from the extension period of TOUCHSTONE, with ≥4 years of follow-up. METHODS: Patients in TOUCHSTONE received placebo or ozanimod (0.5 mg or 1 mg daily) during the 8-week induction and 24-week maintenance periods and could enter the optional open label extension (OLE) with ozanimod 1 mg/day if they were nonresponders at the end of the induction period, lost response during the maintenance period, or completed the maintenance period. Eligible patients entered the OLE between May 2013; March 2015. In 2019, the OLE was ended and all active patients who consented rolled over to a phase 3 program. During the OLE, patients were followed for safety and efficacy at weeks 4, 8, 12, and 12-week intervals thereafter. Partial Mayo score (pMS, comprised of stool frequency, rectal bleeding, and physician’s global assessment subscores) was assessed at all visits. Endoscopy was performed approximately annually in patient subsets, mainly at OLE weeks 56 and 104 per protocol amendments; total Mayo score (tMS, including pMS subscores plus endoscopy), endoscopic improvement (endoscopic subscore of ≤1), and histologic remission (Geboes score 1). Biomarkers of disease activity were assessed (C-reactive protein [CRP], all visits; fecal calprotectin [FCP], OLE week 8, end of study). RESULTS: Of 170 patients entering the OLE, 123 (72%), 102 (60%), 84 (49%), and 71 (42%) completed OLE weeks 56, 104, 152, and 200, respectively. Using non-responder imputation (NRI) for missing data, pMS clinical response and remission rates at week 56 were 71% and 55%, and 41% and 37%, respectively, at week 200. tMS clinical response and remission rates (observed case analysis) were 83% and 40%, respectively, at week 56, and 82% and 41% at week 104. Observed pMS decreased substantially over time, plateauing at 1. Treatment-emergent adverse events (TEAEs) were UC flare (4%), anemia (1%), and ischemic stroke (1%); no serious TEAEs of cardiac arrhythmias or macular edema were reported. CONCLUSION: Data from the TOUCHSTONE OLE demonstrate durable efficacy by clinical, endoscopic, histologic, and biomarker measures with ozanimod 1 mg/day. No new safety risks were identified with ≥4 years of follow-up.

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