Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results From the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study

Abstract

Background and Aims This analysis examined the long-term safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis [UC] with ≥ 4 years of follow-up in the phase 2 TOUCHSTONE open-label extension [OLE]. Methods Patients receiving placebo or ozanimod HCl 0.5 mg or 1 mg during the double-blind period could enter the OLE [ozanimod HCl 1 mg daily]. Partial Mayo score [pMS] clinical response and remission were assessed through OLE week 200 and summarized descriptively using observed cases [OC] and non-responder imputation [NRI]. Endoscopy was required at OLE week 56 and the end of treatment. Parameters associated with endoscopy were summarized at weeks 56 and 104 [OC], and week 56 [NRI]. C-reactive protein and faecal calprotectin were assessed. Adverse events were monitored throughout the study. Results Of 197 patients receiving double-blind treatment, 170 entered the OLE. Discontinuation rates were 28% at year 1 and 15–18% annually through year 4. Partial Mayo measures indicated clinical response and remission rates at OLE week 200 of 93.3% and 82.7%, respectively, using OC and 41% and 37% with the more conservative NRI analysis. At weeks 56 and 104, respectively, histological remission rates were 46.3% and 38.5%, and endoscopic improvement rates were 46.4% and 46.5% [OC]. No new safety signals were identified during ≥ 4 years of follow-up. Conclusions There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126]

An Overview of the Efficacy and Safety of Ozanimod for the Treatment of Relapsing Multiple Sclerosis

“…Ozanimod 0.5 mg did not show a statistically significant benefit. An open-label extension study, 55 with all patients treated with ozanimod 1 mg/d, showed rapid improvement in Mayo scores for patients who switched from the placebo or ozanimod 0.5 mg/d. Long-term benefit with ozanimod 1 mg daily was displayed in patients with moderate-to-severe ulcerative colitis both on clinical and histologic measures.…”

Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs

“…Fingolimod (FTY720), an agonist for S1PRs (S1PR1, S1PR3, S1PR4, and S1PR5), has been approved for multiple sclerosis (MS) by the FDA, showing anti-tumor effects in CRC mouse models [ 30 ]. Ongoing clinical trials (TOUCHSTONE study) also claimed that ozanimod, a highly selective agonist for S1PR1 and S1PR5, showed favorable therapeutic effectiveness for ulcerative colitis (NCT01647516, NCT02531126) [ 177 , 178 ]. It is well established that patients with long-standing ulcerative colitis can develop CRC [ 81 ].…”

Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment

“…Ozanimod has been shown to reduce inflammation and disease parameters in three models of autoimmune disease, including colitis [136]. The results of open-label extension (OLE) of the TOUCHSTONE clinical trial in patients with moderate to severe ulcerative colitis demonstrated that ozanimod has significant benefits and long-term efficacy based on clinical, endoscopic and biomarker measures for up to 4 years of treatment [147]. Endoscopic, histological and clinical improvement was also observed within 12 weeks after initiation of ozanimod in STEPSTONE clinical trial in patients with moderately to severely active Crohn's disease [148].…”