Safety and efficacy of long-term treatment with ozanimod, and oral S1P receptor modulator, in moderate to severe ulcerative colitis: Touchstone extension

Introduction: Ozanimod (RPC1063) is an oral, selective sphingosine 1‐phosphate (S1P) 1 and 5 receptor modulator in clinical development for the treatment of Inflammatory Bowel Disease (ulcerative colitis [UC] and Crohn's disease) and relapsing multiple sclerosis. The objective of the open‐label extension (OLE) of the TOUCHSTONE trial is to evaluate the long‐term efficacy and safety of daily 1 mg ozanimod in patients with moderate to severe UC who had initially participated in the TOUCHSTONE trial. Aims & Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1mg (n=67), or placebo in the TOUCHSTONE trial. Of the initial 197 patients randomized 170 (86%) entered the OLE and received daily 1 mg ozanimod with 109 (64%) remaining in the OLE as of the data cut‐off (March 2016). At the data cut‐off, all remaining patients had received treatment in the OLE for ≥1 year. Results: At entry into the OLE, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg was 4.6, 4.5, and 3.3 respectively. At the time of the data‐cut in the OLE, the pMS had improved in all groups (1.7, 1.7, and 1.9) at Week 44. The greatest improvement was reported in patients who received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial with a change in pMS at Week 44 of ‐2.6, ‐2.7 and ‐1.3 in the placebo, 0.5 mg and 1 mg groups. Improvement occurred rapidly, in the first 4 to 8 weeks of the OLE. The greatest improvement was reported for patients who received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial with a change in pMS at Week 4 of ‐1.8, ‐1.5 and ‐0.8 and a change in pMS at Week 8 of ‐2.4, ‐1.9 and ‐1.1 in the placebo, 0.5 mg and 1 mg groups. At the Week 44 visit in the OLE, 119/131 (90.9%) had little or no active disease based on the physician global assessment (PGA 0 or 1), 129/ 131 (98.4%) had little or no blood in their stools (rectal bleeding subscore [RBS] 0 or 1), 111/131 (84.7%) had no blood in the stools (RBS 0), and 105/131 (80.2%) had little or no increase in their number of stools (Stool Frequency subscore of 0 or 1). The most common adverse events (AEs) (>2.0%) during OLE were UC flare, anemia, upper respiratory tract infection, nasal pharyngitis, back pain, arthralgia, headache, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation. The only serious AEs in ≥2 patients were anemia, and ulcerative colitis flare. ALT and AST 4 3x upper limit of normal occurred in 4 (2.4%) of the 170 patients in the OLE. All elevations were asymptomatic, <5xULN, transient, and resolving while receiving continued treatment. Conclusion: Long‐term treatment with ozanimod continues to be safe and well tolerated with good compliance and evidence of durable efficacy.