Ozanimod is an oral sphingosine-1-phosphate (S1P) receptor modulator that is approved in the United States and the European Union for the treatment of moderately to severely active ulcerative colitis (UC).1,2 The phase 3 True North trial evaluated the safety and efficacy of ozanimod (0.92 mg [equivalent to ozanimod HCl 1 mg], once daily) vs placebo in patients with moderately to severely active UC.3 The double-blind 52-week trial achieved its primary endpoint, demonstrating a significant improvement in the proportion of patients who achieved clinical remission with ozanimod vs placebo, both after 10 weeks of induction (18.4% vs 6.0%; P<.001) and after 42 weeks of maintenance (37.0% vs 18.5%, among patients with a response at week 10; P<.001).
The 2022 Advances in Inflammatory Bowel Diseases conference included 4 posters featuring studies from the True North trial.4-7 A post hoc study evaluated the effect of ozanimod discontinuation on the time to disease relapse.4 The study included patients who received ozanimod during induction and were then randomized to maintenance therapy through week 52 with either ozanimod (n=230) or placebo (n=227). Patients who received continuous ozanimod therapy during induction and maintenance were significantly less likely to relapse than patients who received ozanimod induction followed by placebo (nonrelapse rate at week 42 of maintenance, 86.1% with ozanimod vs 62.6% with placebo; P<.0001). Subgroup analysis further underscored the superior time to disease relapse achieved with ozanimod vs placebo, both in patients with a full clinical remission at week 10 (nonrelapse rate, 90.9% vs 67.9%; P<.001) and in patients with a clinical response without full clinical remission at week 10 (nonrelapse rate, 83.4% vs 59.7%; P<.0001).
A 2-year interim analysis assessed the safety and efficacy of ozanimod in True North participants who received 98 weeks of continuous ozanimod therapy.5 The analysis included patients who demonstrated a clinical response after 52 weeks of continuous ozanimod therapy and were entered into the open-label extension (OLE) study. The results at week 46 of the OLE study showed numerically superior outcomes in patients in clinical remission vs patients with clinical response only at week 52 in terms of clinical remission (73% vs 55%), clinical response (98% vs 95%), endoscopic improvement (82% vs 58%), and corticosteroidfree remission (71% vs 50%). In the overall population of patients with a clinical response who received continuous ozanimod therapy, the mean partial Mayo score stabilized by week 18 (mean Mayo score, 1.3 points) and was maintained through OLE week 46 (mean, 0.9 points). No new safety concerns emerged from the extended observations.
A post hoc analysis evaluated the efficacy of ozanimod among True North patients who were previously exposed to vedolizumab.6,8 The efficacy of ozanimod was evaluated at the end of induction (week 10) and maintenance (week 52). The results suggested that prior exposure to vedolizumab did not affect ozanimod efficacy. At week 10, ozanimod was superior to placebo for all endpoints examined, including symptomatic remission (15.9% vs 8.6%), clinical remission (4.8% vs 2.9%), clinical response (28.6% vs 20.0%), and endoscopic improvement (12.7% vs 5.7%). At week 52, ozanimod was again superior based on all endpoints examined, including symptomatic remission (54.5% vs 13.6%), clinical remission (39.4% vs 4.5%), clinical response (57.6% vs 22.7%), and endoscopic improvement (39.4% vs 9.1%).
A post hoc analysis of True North patient outcomes based on age group demonstrated similar efficacy with ozanimod in patients aged less than 60 years vs patients aged 60 years or greater, based on clinical remission, clinical response, endoscopic improvement, or mucosal healing at week 52 of the study.7 Ozanimod exposure in elderly patients was not associated with new safety concerns, nor were rates of adverse events (AEs) higher in the cohort of older patients than in the cohort of younger patients.
References
- Scott FL, Clemons B, Brooks J et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173(11):1778–1792. doi: 10.1111/bph.13476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeposia [ozanimod] prescribing information. Bristol Myers Squibb; Princeton, NJ; 2022.
- Sandborn WJ, Feagan BG, D’Haens G et al. True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280–1291. doi: 10.1056/NEJMoa2033617. [DOI] [PubMed] [Google Scholar]
- Sands BE, Abraham B, Bressler B Duration of response after ozanimod withdrawal: phase 3 True North study results. Presented at the Advances in Inflammatory Bowel Diseases Conference; Orlando, Florida; December 5-7, 2022. Poster 14.
- Abreu MT, Dulai P, Dignass A Interim analysis of 2 years of continuous ozanimod treatment from the True North open-label extension study. Presented at the Advances in Inflammatory Bowel Diseases Conference; Orlando, Florida; December 5-7, 2022. Poster 76.
- Sands BE, Jain A, Ahmad HA Efficacy of ozanimod in patients with ulcerative colitis who were previously exposed to vedolizumab: True North post hoc analysis. Presented at the Advances in Inflammatory Bowel Diseases Conference; Orlando, Florida; December 5-7, 2022. Poster 15.
- Khan N, Irving P, Blumenstein I Ozanimod efficacy and safety in older patients with ulcerative colitis: a post hoc analysis from True North. Presented at the Advances in Inflammatory Bowel Diseases Conference; Orlando, Florida; December 5-7, 2022. Poster 98.
- Entyvio [vedolizumab] prescribing information. Takeda Pharmaceuticals USA; Lexington, MA; 2022.