Ozanimod for moderate-to-severe Ulcerative Colitis (UC): efficacy, safety, and histology results from the induction and maintenance periods of the Phase 3 TRUE NORTH Study

Introduction Ozanimod (OZA), an oral sphingosine-1-phosphate (S1P) receptor modulator that selectively targets S1P₁ and S1P_5, demonstrated efficacy and safety in patients (pts) with moderate-to-severe UC in the phase 2 study TOUCHSTONE (NCT01647516).

Objectives TRUE NORTH (NCT02435992), a phase 3 double-blind (DB) study, examined the effects of once daily oral OZA HCl 1mg (equivalent to OZA 0.92mg) induction and maintenance therapy in adults with moderate-to-severe UC.

Methods During the 10 week (wk) induction period, pts (cohort 1) received DB treatment with OZA or placebo (PBO) or open label OZA (cohort 2). Pts with clinical response after OZA induction therapy were re-randomized to DB maintenance treatment with OZA or PBO through wk 52. Clinical remission per 3-component Mayo score was the primary endpoint for both periods. Key secondary endpoints included clinical and histologic remission, clinical response, endoscopic improvement and mucosal healing.

Results 645 pts in cohort 1 were randomized to OZA (n = 429) or PBO (n=216). At wk 10, 18.4 % and 6.0 % of pts in the OZA and PBO groups, respectively, achieved clinical remission (P < 0.0001). All key secondary efficacy endpoints showed statistically greater improvements with OZA vs PBO and a significantly greater proportion of pts achieved histologic remission. In the maintenance period, 457 pts were re-randomized to OZA (n=230) or PBO (n=227); 80.0 % and 54.6 % completed the study. For the primary endpoint, 37.0 % and 18.5 % of pts in the OZA and PBO groups, respectively, achieved clinical remission (P < 0.0001). Secondary endpoints were all statistically significant for OZA vs PBO. The most common treatment-emergent adverse events (AE) were anemia, nasopharyngitis, headache, and increased alanine aminotransferase or gamma-glutamyl transpeptidase. Herpes zoster infections occurred occasionally, none of them were serious, severe, or disseminated. No serious opportunistic infections were reported for OZA and PBO.

Discussion: OZA showed significant benefits on clinical, endoscopic, histologic, and mucosal healing endpoints vs PBO in pts with moderate-to-severe UC for up to 52 wks. No new safety signals were observed.

(adapted from ACG 2020, LB5, Sandborn et al.)

Publication History

Article published online:
07 September 2021