New Drug Class in the Works for Ulcerative Colitis

Caroline Helwick

May 19, 2015

WASHINGTON, DC — Ozanimod, a novel sphingosine 1-phosphate receptor modulator, is safe and effective in the treatment of patients with moderate to severe ulcerative colitis, according to results from the phase 2 TOUCHSTONE study.

"Ozanimod 1 mg induced clinical remission at week 8, the primary end point, and met all three secondary end points," said William Sandborn, MD, from the University of California, San Diego.

"And the favorable benefit–risk profile supports the planned phase 3 trial and the phase 2 study in Crohn's disease," he reported here at Digestive Disease Week 2015.

The drug, an oral S1P receptor of subtypes 1 and 5, is also being evaluated in relapsing multiple sclerosis, Dr Sandborn explained. However, ozanimod has a more favorable safety profile than the SP1 receptor modulator fingolimod, which has been used on more than 100,000 multiple sclerosis patients.

The international 8-week induction trial involved 197 patients with moderate to severe ulcerative colitis, defined as a Mayo score of 6 to 12 and an endoscopy subscore of at least 2. For responders, there was a continuing maintenance period.

Patients were randomized to ozanimod 0.5 mg, ozanimod 1.0 mg, or placebo.

The primary end point was remission at week 8, defined as a Mayo score of 2 or lower and no subscore greater than 1.

The secondary end point of response was defined as a reduction in Mayo score of at least 3 and at least 30%, and a decrease in the rectal bleeding score of at least 1 or a rectal bleeding score of 1 or lower. The other secondary end points were mucosal improvement, defined as an endoscopy subscore of 1 or lower, and change in Mayo score.

The induction portion of the study was completed by 95% of patients.

"A dose–response relationship was observed for all primary and key secondary efficacy end points," Dr Sandborn reported.

The differences between high-dose ozanimod and placebo were significant for clinical response (P = .0207), clinical remission (P = .0482), mucosal improvement (P = .0023), and improvement in Mayo score (P = .0035).

The differences between low-dose ozanimod and placebo were significant for mucosal improvement (P = .0348).

Table 1. TOUCHSTONE Study Outcomes

Outcome Ozanimod 1.0 mg Ozanimod 0.5 mg Placebo
Clinical remission at week 8, % 16.4 13.8 6.2
Clinical response at week 8, % 56.7 53.8 36.9
Mucosal improvement at week 8, % 34.3 27.7 12.3
Improvement in Mayo Score from baseline, points 3.3 2.6 1.9

 

Safety assessments included electrocardiogram, Holter monitoring, pulmonary function testing, optical coherence tomography, and adverse events.

Adverse event profiles were comparable in the three groups, with approximately 31% of patients experiencing a treatment-emergent adverse event in each group.

Table 2. Adverse Events

Adverse Event Ozanimod 1.0 mg, % Ozanimod 0.5 mg, % Placebo, %
Worsening of ulcerative colitis 1.5 3.1 4.6
Anemia or decreased hemoglobin level 0.0 4.6 6.2
Serious treatment-emergent event 1.5 1.5 6.2

 

Three patients receiving ozanimod experienced transient elevations in alanine aminotransferase. There were no significant cardiac, ophthalmologic, or infectious findings.

During a plenary lecture, Maria Abreu, MD, from the University of Miami Health System, expressed optimism about the use of SP1 receptor modulators in ulcerative colitis.

SP1 receptor modulators sequester T-cells, "so they can't get out of the gut," she explained. "Ozanimod basically interferes with the ability of the cells to recognize their way back out of the lymph node."

"Presumably this is a new and improved version of molecules that have been used effectively in multiple sclerosis," she added.

"This is a new class of drug that might work differently from current drugs for inflammatory bowel disease," said Charles Bernstein, MD, from the University of Manitoba in Winnipeg, Canada.

"They've been successful in multiple sclerosis, and both IBD and MS are T-cell-mediated diseases," he told Medscape Medical News. "There's a lot of enthusiasm, therefore, that this may be a class of drug that will be very beneficial. Also, the safety data in TOUCHSTONE look very good.

"We are looking forward to seeing more about this drug," he said.

This study was sponsored by Receptos, the manufacturer of ozanimod. Dr Sandborn receives consulting fees from Receptos. Dr Bernstein and Dr Abreu have disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2015: Abstract 445. Presented May 17, 2015.

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