Ozanimod (RPC-1063) is an investigational therapy being developed by Celgene to treat ulcerative colitis (UC), a form of inflammatory bowel disease (IBD).

An oral “immunomodulator,” or therapy that can result in an adjustment of the immune response, Ozanimod entered into testing as a potential treatment for multiple sclerosis (MS). It is showing positive results in Phase 3 clinical trials for this disease.

How ozanimod works

UC is an autoimmune disease, where the body directs too many cells involved in the immune response (lymphocytes) to the gastrointestinal (GI) tract, also known as the digestive system. This flood of cells results in inflammation (swelling), as well as ulcers and lesions. By suppressing — modulating — the immune system, ozanimod aims to reduce inflammation and allow the GI tract to heal.

Two main proteins are involved in the immune system’s inflammatory response — sphingosine-1-phosphate (S1P)-1 and -5 receptors. They regulate the number of lymphocytes that are released into the blood stream. Ozanimod targets these receptors to be broken down, resulting in fewer lymphocytes available to buildup in the GI tract, reducing or stopping the inflammatory response.

Ozanimod in clinical trials

Touchstone, a multi-center, randomized, double-blind and placebo-controlled Phase 2 clinical trial (NCT01647516) is being carried out in 195 people with ulcerative colitis. Patients receive a daily dose of ozanimod (at either a high, 1 mg, or low, 0.5 mg, dose) or a placebo for 32 weeks. The drug’s effects are evaluated using the Mayo score for UC, with the aim of assessing the proportion of patients in clinical remission after eight weeks, and if this is maintained over the treatment’s remaining course. Results obtained so far have been published in the New England Journal of Medicine, and the trial is expected to finish in December 2019.

At week eight, results showed a significant difference in the number of patients on the 1 mg dose of ozanimod (16 percent) entering clinical remission and those on placebo (6 percent), but not between the 0.5 mg dose group and placebo patients. Both the 1 mg and 0.5 mg doses of ozanimod resulted in a higher proportion of mucosal healing (the complete healing of ulcers and lesions in the gut) compared to placebo (34 percent and 28 percent, respectively, compared to 12 percent in placebo patients). These significant results were maintained after 32 weeks.

Although the 1 mg dose of ozanimod showed promise, researchers concluded that the study was not large enough or of a sufficiently long duration to provide solid evidence on safety or efficacy.

A Phase 3 open-label extension trial (NCT02531126) is currently assessing the safety and efficacy of the 1 mg dose for up to five years in patients with moderate to severe ulcerative colitis who were treated with ozanimod in previous trials. Patient enrollment is ongoing.

Celgene is also carrying out a Phase 2 clinical trial (NCT02531113) assessing the efficacy and safety of ozanimod in patients with Crohn’s disease (CD), another form of IBD. No information on results has yet been announced. The study is expected to be completed in January 2018.

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