Ozanimod Hits Ulcerative Colitis Early

Just 1 week of full-dose ozanimod (Zeposia) was enough to bring symptom relief and biomarker improvement in patients with ulcerative colitis, a new analysis of placebo-controlled trial data indicated.

Differences in rectal bleeding and stool frequency were already evident between patients assigned to the oral drug versus placebo in week 2 of the so-called TRUE NORTH study, said Mark Osterman, MD, of Bristol Myers Squibb (BMS) in Princeton, New Jersey, which makes ozanimod.

Those benefits and others extended through week 10, which was the extent of the current analysis, Osterman told attendees at the Digestive Disease Week (DDW) virtual meeting.

Osterman, who was at the University of Pennsylvania when the trial was conducted, noted that the study began with a 7-day dose up-titration period, such that therapeutic dosing was not reached until week 1.

Topline results from TRUE NORTH’s main endpoints were released in June 2020, showing that clinical remission was achieved by significantly more patients receiving ozanimod versus placebo by week 10, and that this superiority was maintained for 1 year. Subsequent reports gave more details, including that only a small minority of patients achieved remission with the drug (18.4% vs 6% with placebo) at week 10. Remission rates did increase with further treatment, however, and other outcomes such as endoscopic improvement and clinical response favored the drug over placebo.

Ozanimod is a sphingosine-1-phosphate inhibitor, with a mechanism of action believed to involve preventing autoimmune T cells from exiting the lymph system. It was approved last year as a treatment for multiple sclerosis (MS); its potential as a treatment for inflammatory bowel disease (BMS is also testing the agent in Crohn’s disease) makes it unusual, as hardly any drugs have proved safe and effective as disease-modifying agents both in MS and in other autoimmune conditions.

Osterman’s DDW presentation focused on secondary outcomes in TRUE NORTH during the 10-week induction phase: scores for rectal bleeding and stool frequency and levels of fecal calprotectin (FCP) and C-reactive protein (CRP). The latter two are biomarkers of colitis disease activity.

Just under 650 patients with moderate to severe ulcerative colitis were randomized 2:1 to ozanimod or placebo in TRUE NORTH. (The study also included a second cohort given open-label ozanimod for the initial 10 weeks, who were not included in Osterman’s analysis). Patients’ mean age was about 42, who had been living with the condition for almost 7 years on average. Baseline mean scores for rectal bleeding and stool frequency were 1.7 and 2.4, respectively. FCP and CRP levels at baseline varied substantially among participants but averaged somewhat more in the placebo group than in those assigned to ozanimod.

By study week 2, the ozanimod group showed a mean decline in stool frequency score of about 0.37 points, compared to a 0.28-point drop for the placebo group. The gap widened in later weeks, reaching 0.35 points at week 10.

Rectal bleeding scores showed a similar pattern: declining almost 0.6 points with ozanimod versus 0.4 points with placebo at week 2, and the difference reaching 0.5 points by week 10.

About 50% of the ozanimod group had “meaningful” improvement in rectal bleeding at week 10, compared with 30% of the placebo group, Osterman reported. For stool frequency, the corresponding values were 42% and 27%, respectively. Meaningful improvements in both outcomes were achieved by 35% of the ozanimod group versus 19% of the placebo group (P=0.0001).

Ozanimod led to substantial declines in FCP and CRP levels, whereas no change in either was seen in the placebo group.

BMS is now seeking an ulcerative colitis indication for ozaminod, largely on the strength of TRUE NORTH, with the FDA expected to decide by the end of this month.

Last Updated May 23, 2021