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MS Drug Candidate Shows Promise for Treatment of Ulcerative Colitis

Sphingosine 1-phosphate receptor modulator achieves clinical remission

Positive clinical data have been reported on a drug candidate for ulcerative colitis that was first discovered and synthesized at the Scripps Research Institute.

According to results from a phase II study of 199 patients with active moderate-to-severe disease, the drug candidate RPC1063 (Receptos, Inc.) has the potential to significantly improve the treatment paradigm for patients with ulcerative colitis. The latest results show that, after 8 weeks of treatment with a 1-mg dose of RPC1063, 16.4% of patients were in clinical remission compared with 6.2% of patients given placebo.

Ulcerative colitis is a chronic condition that involves inflammation and sores in the inner lining of the digestive tract. The disorder is an inflammatory bowel disease that, along with Crohn’s disease, affects more than 1 million people in the U.S., according to the Centers for Disease Control and Prevention. Some people have mild disease, whereas others have life-threatening complications.

While existing medications for ulcerative colitis do help some patients, 23% to 45% of people with the disease progress and eventually require surgical removal of all or part of the colon, according to the Crohn’s and Colitis Foundation of America.

RPC1063 was derived from a screening “hit” in the National Institutes of Health molecular library at Scripps Florida’s Molecular Screening Center, using assay technology from the Scripps lab in La Jolla, California. The two centers then developed medicinal chemistry to turn that "hit" into a validated lead, and then ultimately a drug candidate.

The latest results come from a multi-national, double-blind, randomized, placebo-controlled study investigating the effect of two active doses of RPC1063 (0.5 mg and 1.0 mg) compared with placebo for the treatment of moderately to severely active ulcerative colitis in a total of 199 patients.

The study’s primary endpoint –– the proportion of patients in clinical remission at week 8, as defined by the industry-standard Mayo scoring criteria –– was achieved by 16.4% of patients receiving the 1.0-mg dose of RPC1063 compared with 6.2% of patients receiving placebo (P < 0.05). In the low-dose group of 0.5 mg, 13.8% of patients achieved clinical remission, which was not statistically significantly different from the placebo group.

All secondary endpoints at week 8, including the patient’s clinical response, the change in the Mayo score, and mucosal improvement on endoscopy, were also positive and statistically significant for the 1.0-mg dose compared with placebo. Notably, 58.2% of patients receiving the 1.0-mg dose of RPC1063 achieved a clinical response compared with 36.9% of the placebo group (P < 0.05).

In light of these positive results, a phase III trial is being planned for RPC1063 in patients with ulcerative colitis, as well as a phase II study of the drug candidate for Crohn’s disease.

The mechanism of action of RPC1063 –– sphingosine 1-phosphate receptor modulation –– may also be useful in the treatment of other autoimmune diseases. The drug candidate is currently being evaluated for the treatment of multiple sclerosis in a phase III study.

Sources: Scripps Research Institute; October 27, 2014; and Receptos; October 27, 2014.

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