Positive Results Announced for Investigational Ulcerative Colitis Drug

Treatment with ozanimod associated with decreased partial Mayo scores in inflammatory bowel disease.

Celgene recently announced results from an extension of the phase 2 clinical trial TOUCHSTONE, which evaluated ozanimod in patients with moderate-to-severe ulcerative colitis.

The results were presented in full at the United European Gastroenterology Week and at the American College of Gastroenterology Annual Scientific Meeting.

“Since ulcerative colitis is a chronic condition, patients are looking for treatments that can help them over the long term,” said William Sandborn, MD. “These encouraging findings suggest that continued treatment with ozanimod shows evidence of durable efficacy with an acceptable safety profile.”

Ozanimod is an investigational selective sphingosine 1-phosphate 1 and 5 receptor modulator that was designed for immune-inflammatory conditions, such as inflammatory bowel disease and relapsing multiple sclerosis. The drug is thought to interfere with sphingosine 1-phospate signaling to prevent lymphocytes from contributing to tissue inflammation, according to Celgene.

There were 197 patients with moderate-to-severe ulcerative colitis included in the first part of the trial, which investigated the efficacy and safety of ozanimod compared with placebo at 8 weeks. Patients who achieved a response at week 8 continued the treatment through 32 weeks.

The primary endpoint of the trial was the amount of patients who achieved remission at 8 weeks. Secondary endpoints included the amount of patients who achieved a clinical response and had mucosal improvement.

The change from baseline Mayo score, an assessment of disease activity, was also a secondary endpoint. TOUCHSTONE reached its endpoints, especially among patients receiving a 1-mg dose of ozanimod compared with placebo.

All participants were entered into the open-label extension if they were unresponsive to treatment, relapsed during the maintenance phase, or completed the maintenance phase, according to Celgene. There were a total of 170 patients included, and the goal of the extension was to determine the long-term efficacy and safety of daily treatment with 1 mg of ozanimod.

Investigators found that all patients had decreased mean partial Mayo Scores. For patients who were originally treated with 0.5-mg of ozanimod, mean scores decreased from 4.5 to 1.7 at 44 weeks. For patients who received initial treatment with 1-mg of ozanimod, mean scores decreased from 3.3 to 1.9.

For patients initially in the control group, mean scores decreased from 4.6 to 1.7 at 44 weeks. There was also a decrease in occurrences of rectal bleeding and moderate or severe diarrhea during the extension phase, Celgene reported.

The most common adverse events were ulcerative colitis flare, upper respiratory tract infection, anemia, nasopharyngitis, transaminase elevation, back pain, arthralgia, and headache. No cardiac, ophthalmologic, or infectious adverse events were experienced.

Serious adverse events, including anemia and ulcerative colitis flare, were experienced by 9.4% of patients.

There were also 2.4% of patients who had alanine aminotransferase and aspartate aminotransferase elevations more than 3 times the normal limit. The increases were asymptomatic, and able to be resolved during treatment.

“Findings from this extension study at week 44 showed improvements in efficacy measures for patients who took ozanimod throughout both the blinded study and the extension,” said Scott Smith, president, Celgene Inflammation & Immunology. “We recognize the strong need for innovative treatments that help patients with inflammatory bowel disease achieve durable results. We are committed to advancing additional transformational oral treatment options for these patients.”