Endoscopic and Clinical Efficacy Demonstrated with Oral Ozanimod in Active Crohnʼs Disease in Biologic-Naïve and Biologic Experienced Patients

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BACKGROUND: Ozanimod, an oral, once-daily immunomodulator that selectively targets S1P1R and S1P5R, has demonstrated efficacy in ulcerative colitis (UC) (Sandborn NEJM 2016) is being evaluated in patients with active Crohn's Disease (CD). This Phase 2 open-label study examined endoscopic and clinical outcomes following treatment with ozanimod 1 mg daily for 12 weeks in biologic-naïve and biologic-experienced CD patients. METHODS: Patients with active CD defined as Crohn's Disease Activity Index [CDAI] score 220-450 and simple endoscopic score for CD [SES-CD] ≥6 (isolated ileum disease SES-CD ≥4), were dosed daily with ozanimod 1 mg. Endoscopic assessments were read by an imaging core lab in a blinded manner. Daily electronic diary records were used to collect CD symptoms (including abdominal pain and soft/loose stool frequency). SES-CD was evaluated at baseline and Week 12, and CDAI was assessed at baseline, Weeks 4, 8, 12. RESULTS: Sixty-nine patients were enrolled and treated. At baseline, mean age was 37.7 years, mean SES-CD was 13.3, and mean CDAI was 320. Mean CD duration was 10.0 years, with 54% of patients having had prior exposure to biologic therapy (i.e., TNF-α, vedolizumab). Patients with available data at baseline and Week 12 were included in the analyses, including SES-CD matched endoscopic segments (n=60 patients; 27, biologic-naïve; 33, biologic-experienced) and CDAI (n=59). Overall, reductions from baseline of ≥25% and ≥50% in SES-CD score were seen in 43.3% and 26.7% of patients, respectively. Reductions from baseline of ≥25% and ≥50% in SES-CD score were seen in 48.1% and 33.3% of biologic-naïve patients, and 39.4% and 21.2% of biologic-experienced patients, respectively Overall, CDAI response (CDAI decrease ≥100) was demonstrated in 66.1% of patients and CDAI remission (CDAI <150) was demonstrated in 45.8% of patients at Week 12. In biologic-naïve patients, CDAI response was demonstrated in 74.1% of patients and CDAI remission was demonstrated in 63.0% of patients. In biologic-experienced patients, CDAI response and remission rates were 59.4% and 31.3%, respectively. Adverse event and serious adverse event rates were predominantly related to underlying Crohn's disease with no specific drug attributable serious adverse events demonstrated. The overall safety profile in CD was similar to that observed in UC. CONCLUSION(S): In this open-label study, ozanimod therapy demonstrated meaningful clinical and endoscopic improvements at Week 12 in both biologic-naïve and biologic-experienced patients with moderate to severe CD. No drug-specific safety signals were identified.