Oral Ozanimod Shows Improvements in Ulcerative Colitis

Histologic improvement greater with experimental drug versus placebo in patients with moderate-to-severe ulcerative colitis.

Histologic improvement was found in patients with moderate-to-severe ulcerative colitis who were taking ozanimod in a phase 2 trial.

Ozanimod is an investigational selective sphingosine 1-phosphate 1 and 5 receptor modulator in development for immune-inflammatory indications, including inflammatory bowel disease (IBD) and multiple sclerosis (MS).

During the TOUCHSTONE phase 2 clinical trial, participants were administered a daily dose of 0.5 mg (n=65), 1 mg of ozanimod (n=67), or a placebo (n=65) to evaluate safety and efficacy after 8 weeks of treatment.

“It's exciting to observe histologic improvements in patients with ulcerative colitis who were treated with ozanimod,” said William Sandborn, MD. “Clinical research suggests that histologic improvements can be linked with improved clinical outcomes in ulcerative colitis. “While often more difficult to measure, endpoints such as histologic improvement or remission are emerging as important treatment goals for patients and their physicians.”

In the study, 197 patients with moderate-to-severe ulcerative colitis were enrolled. Patients who were able to meet a clinical response by week 8 continued to take their original treatment through week 32 in a maintenance phase.

The primary endpoint was the amount of patients who were in remission at week 8 and the secondary endpoints were the portion of patients who achieved a clinical response, who had mucosal improvement, and a change from baseline in Mayo score.

The results of the histology in the TOUCHSTONE study were determined by the assessment in the change from baseline in Geboes score (12.92 in ozanimod 1-mg, 14.36 in ozanimod 0.5-mg and 13.94 placebo; a decrease in absolute score indicates an improvement) was found to be significantly greater for the 1-mg dose compared to the placebo at week 8 [Geboes (-4.37 vs. -2.20, p=0.0345)] and week 32 [Geboes (-5.50 vs. -2.24, p=0.0033)].

Additionally, the 0.5-mg dose showed a greater improvement than placebo, but the difference didn’t reach statistical significance. Adverse events occurred in 38.8% of patients in the ozanimod 1-mg group, 40% in the 0.5-mg ozanimod group, and 40% in the placebo group.

The most common adverse events were worsening ulcerative colitis in 3, 2, and 5 patients, respectively, followed by anemia in 0, 3, and 4 patients, respectively.

“These data suggest that in addition to benefits we've previously seen, oral ozanimod could also help ulcerative colitis patients achieve the important treatment goal of histologic remission,” said President of Celgene Inflammation & Immunology Scott Smith. “We are committed to bringing innovative medicines and different treatment options for patients with inflammatory bowel disease and continue to actively advance the phase 3 clinical program for ozanimod.”