Long-Term Clinical, Endoscopic, and Symptomatic Outcomes of Treatment With Ozanimod: Interim Analysis of the True North Open-Label Extension Study

Ozanimod is a selective S1P¹,⁵ receptor modulator that was shown to be effective and safe for the treatment of patients with moderately to severely active UC in the phase 3 True North trial.¹ Two presented posters summarized data from an interim analysis of the True North open-label extension study.

The objective of the first study, presented by Afzali and colleagues, was to evaluate the durability of ozanimod efficacy (up to week 94 in the open-label study) among patients who were clinical responders and who did and did not achieve clinical remission at week 52 in True North.² At the time of data cutoff, all 83 clinical responders/remitters and 43 patients who were clinical responders/nonremitters had completed week 94 of the open-label extension study or discontinued the study. This interim analysis found that, compared with clinical responders/ nonremitters, more clinical responders/ remitters achieved all the endpoints evaluated at weeks 46 and 94 of the open-label extension trial. This was true for both the OC and the NRI analysis. In the OC analysis at week 94, 75.9% of clinical responders/remitters had achieved clinical remission compared with 55.6% of clinical responders/nonremitters (Figure 7). Further, 94.4% of clinical responders/remitters had achieved clinical response at week 94 vs 85.2% of clinical responders/nonremitters. In addition, higher proportions of clinical responders/remitters achieved and maintained endoscopic improvement and corticosteroid-free remission for an additional 2 years compared with clinical responders/ nonremitters. Discontinuations owing to TEAEs occurred in 4.8% of clinical responders/remitters and in 8.3% of clinical responders/nonremitters.

Figure 7.

Remission and response rates in the OC analysis and NRI analysis of ozanimod treatment at OLE weeks 46 and 94 in patients with moderately to severely active ulcerative colitis from the phase 3 True North study.

^aDenominators for the OC analyses were based on the numbers of patients who completed OLE week 46 or OLE week 94 and had data available for the endpoints in question.

^bDenominators for the NRI analyses were based on the numbers of patients who completed OLE week 46, completed OLE week 94, or discontinued ozanimod treatment. OC, observed case; OLE, open-label extension; NRI, nonresponder imputation.

Adapted from Afzali et al. Abstract P0675. Presented at: ACG 2023; October 20-25, 2023; Vancouver, Canada.²

The second study, presented by Abreu and colleagues, investigated whether achievement of increasingly objective endpoints at week 52 of True North impacted the durability of symptomatic and clinical outcomes in patients treated with continuous ozanimod throughout the open-label extension study.³ These endpoints included clinical remission, endoscopic improvement, endoscopic remission, histologic remission, mucosal healing, and stringent mucosal healing. The investigators concluded that, in the open-label extension trial, maintenance of clinical response, clinical remission, and corticosteroidfree remission was not significantly impacted by achievement of endpoints of increasing objectivity. However, they found that achievement of clinical remission to warrant entry into the open-label extension trial had an incremental benefit over achievement of clinical response for the outcomes of maintenance of clinical remission and corticosteroid-free remission at both week 46 and week 94. Overall, clinical outcomes were sustained from week 46 to week 94 of the open-label extension, regardless of the endpoint achieved at study entry. Symptomatic clinical response was maintained throughout the open-label extension study, with continued response at week 94 in greater than 92% (by OC analysis) of patients in all groups at entry. Additionally, improvements in both RBS and SFS were sustained through week 94 regardless of the patient disposition at entry into the open-label extension.