Efficacy and Safety of 2 Years of Continuous Ozanimod Treatment: Interim Analysis of the True North Open-Label Extension Study

Introduction: The phase 3 True North (TN) study demonstrated the efficacy and safety of oral ozanimod (OZA) 0.92 mg once daily (equivalent to OZA HCl 1 mg) in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) study is exploring longer-term efficacy and safety of OZA in UC. This interim analysis of the TN OLE evaluated the efficacy and safety of OZA in pts who received 98 weeks of continuous OZA treatment. Methods: Pts in clinical response (CRS) after 52 weeks of continuous OZA during TN who rolled over into the OLE were included (data cutoff: September 30, 2020). Nearly 73% of pts had completed OLE Week 46 (Week 98 of continuous OZA therapy) at the time of data cutoff when outcomes were measured. Endoscopy was performed annually throughout the OLE and was scored by Mayo endoscopic score. Efficacy data (Clinical Remission [CRM], CRS, Endoscopic Improvement [EI], and Corticosteroid-Free Remission [CFR]) were analyzed using observed cases (OC) and nonresponder imputation (NRI). Safety data were also recorded. Results: Of 131 total pts in CRS at TN Week 52, 83 (63%) were in CRM and 48 (37%) were in CRS only (but not CRM) on entry to the OLE. Demographic and clinical characteristics at TN baseline were similar for pts in both subgroups, except that a higher proportion of pts with only CRS at OLE entry were exposed to prior immunomodulators or tumor necrosis factor inhibitors at TN baseline. A high proportion of the overall population sustained CRM, CRS, EI, and CFR on OZA at OLE Week 46 in both OC and NRI analyses, with higher rates of CRM, EI, and CFR among pts entering the OLE in CRM (Table). Notably, 97% of all pts sustained CRS through overall Week 98 in OC analysis (64% in NRI analysis). Of the pts in CRS only at OLE entry, 55% achieved CRM by OLE Week 46 in OC analysis (NRI: 32%). Mean partial Mayo score over time for the overall population is shown in the Figure. No new safety findings emerged from this extended analysis; 1 sudden death occurred during the OLE and was adjudicated to be unrelated to OZA. Conclusion: This interim analysis of the TN OLE found that pts who achieved CRS or CRM after 1 year of OZA had a high rate of sustaining CRS, CRM, and EI for another year. Pts who after a year of OZA were in CRS could achieve CRM with continued OZA therapy. No additional safety signals were observed.Figure 1.: Mean partial Mayo scores of OZA over time in the overall population of pts in CRS at TN Week 52 Table 1. - OZA efficacy at OLE Week 46 (overall Week 98) in pts entering OLE in CRS (OC and NRI data) Clinical endpoints at OLE Week 46,% (n/N) Overall population at TN Week 52 (n=131) Pt subgroup in CRM a at TN Week 52 (n=83) Pt subgroup in CRS b only at TN Week 52 (n=48) OC c NRI d OC c NRI d OC c NRI d Clinical Remission 67 (42/63) 44 (42/95) 73 (30/41) 53 (30/57) 55 (12/22) 32 (12/38) Clinical Response 97 (61/63) 64 (61/95) 98 (40/41) 70 (40/57) 95 (21/22) 55 (21/38) Endoscopic Improvement e 74 (55/74) 58 (55/95) 82 (41/50) 72 (41/57) 58 (14/24) 37 (14/38) Corticosteroid-Free Remission f 63 (40/63) 42 (40/95) 71 (29/41) 51 (29/57) 50 (11/22) 29 (11/38) aCRM was defined as RBS = 0 and SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS) and mucosal endoscopy subscore ≤1 without friability.bCRS was defined as reduction of 3-component Mayo score of ≥2 points and at least 35%, and reduction in RBS of ≤1 point or an absolute RBS of ≤1.cDenominators for OC were based on the number of pts who completed Week 46.dDenominators for NRI were based on the number of pts who completed Week 46 of the OLE and those who withdrew before Week 46 but would have reached Week 46 if they had stayed. This did not include the number of pts in the OLE who have not yet completed Week 46 or who discontinued and would not have reached Week 46 by this data cutoff.eEndoscopy subscore of ≤1 point.fClinical remission while off corticosteroids for ≥12 weeks.CRM, clinical remission; CRS, clinical response; CRS only, clinical response but not remission; RBS, rectal bleeding subscore; SFS, stool frequency subscore.