Ozanimod, an Oral S1P Receptor Modulator, Is Effective and Well-Tolerated in the Long-Term Treatment of Moderate to Severe Ulcerative Colitis

Abstract

BACKGROUND: Ozanimod, an oral, once-daily immunomodulator that selectively targets S1P1R and S1P5R, has demonstrated clinical efficacy in UC for induction and maintenance therapy in the TOUCHSTONE trial (Sandborn NEJM 2016). The objective of the open-label extension (OLE) of the TOUCHSTONE trial is to evaluate long-term efficacy and safety of daily 1 mg ozanimod in patients with moderate to severe UC who had initially participated in TOUCHSTONE for up to 32 weeks. METHODS: In TOUCHSTONE,197 patients were randomized (1:1:1) and treated with placebo (n=65), ozanimod 0.5 mg (n=65), or 1 mg (n=67). 170 (86%) entered the OLE. Efficacy data are reported as observed through Week 104 and safety includes all events through the data cut-off of March 2017. RESULTS: At OLE entry, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1 mg was 4.6, 4.5, and 3.3 respectively, which improved rapidly by OLE Week 4 (-1.7, -1.5 and -0.8), and further improved through OLE Week 8 (–2.3, –1.9 and –1.1). Improvement was sustained up to OLE Week 104 (-2.3, -2.2 and -0.9). Improvement with ozanimod 1 mg was seen in all groups, with the greatest improvement reported in patients who had received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial. All three groups achieved similar long-term improvement in pMS. The rectal bleeding score (RBS) improved rapidly in all groups, particularly in patients who had received placebo prior to OLE: based on observed cases, at OLE entry, 30.9% had no blood in their stools (RBS 0), and 67.3% had RBS ≤1; at OLE Weeks 4 and 8, 66.0% and 76.9% had RBS=0; and 94.3% and 98.1% had RBS ≤1. The effect on rectal bleeding was sustained through OLE Week 104; in all patients combined who remained on ozanimod, 88.2% reported a RBS=0 and 98.7% reported a RBS ≤1, at OLE Week 104. AEs and SAEs were reported in 50.0% and 11.1% patients. The only SAEs in ≥2 patients were anaemia, and ulcerative colitis flare. ALT and AST >3x ULN occurred in 2.9% of patients. All elevations were asymptomatic, <5xULN, transient, and resolving while receiving continued treatment. CONCLUSION(S): Long-term treatment with 1 mg ozanimod appears to be well tolerated with evidence of rapid onset and durable efficacy.