Ozanimod Shows Potential for Crohn's Disease, Ulcerative Colitis

Celgene Corporation recently announced that data from a phase 2 clinical trial exploring ozanimod in Crohn’s disease (CD) and ulcerative colitis (UC) will be presented at the World Congress of Gastroenterology at ACG2017, according to a press release.

The presentations will feature results from the STEPSTONE study and the open-label extension of the TOUCHSTONE study, which included patients with moderate-to-severe CD and UC, respectively.

Ozanimod is an investigational sphingosine 1-phosphate (S1P) 1 and 5 receptor modulator that is also being evaluated in multiple sclerosis.

"The new STEPSTONE findings further validate our hypothesis of ozanimod in Crohn's disease and the latest data from the TOUCHSTONE study continue to support the potential of ozanimod to provide continued efficacy in ulcerative colitis at 92 weeks," said Terrie Curran, president, Celgene Inflammation and Immunology. "The results in both studies are highly encouraging as we execute pivotal studies of ozanimod in Crohn's disease and ulcerative colitis in hopes of advancing oral treatment options for these patients."

The STEPSTONE trial assessed the efficacy ozanimod 1-mg daily in 69 patients with CD after 12 weeks of therapy. The investigators explored the simple endoscopic score for CD (SES-CD) matched intestinal segments and the analysis of CD activity index (CDAI), according to the release.

The researchers found that 27% of patients had SES-CD score reductions of least 50% and 43% experienced at least a 25% reduction.

Notably, patients who had shorter disease duration were observed to have a more significant endoscopic response, with 36% of patients seeing a 50% reduction and 36% of patients seeing a 25% reduction, according to the study.

Additionally, patients with lower baseline endoscopic disease activity had a greater endoscopic response, with 30% of patients achieving a 50% reduction and 49% achieving a 25% reduction.

CDAI score reductions were observed at week 4 and persisted through week 12, with 66% of patients achieving a response and 46% of patients achieving remission at week 12, according to the study.

Common adverse events included CD flare, abdominal pain, nausea, lymphopenia, arthralgia, vomiting, increased gamma-glutamyl transpeptidase, urinary tract infection, paresthesia, anal abscess, and increased alanine aminotransferase.

"Improvements in endoscopy are thought to correlate with long-term benefits for patients with Crohn's disease, a chronic condition in which patients are regularly seeking out additional options to manage their disease," said Brian G. Feagan, MD, Robarts Clinical Trials and the University of Western Ontario. "The endoscopic, clinical improvement and the safety profile of ozanimod reported in the STEPSTONE study are encouraging and support its further development as a potential oral option for patients with Crohn's disease."

Celgene will also report data from the 92-week TOUCHSTONE extension trial, which investigated the safety and efficacy of ozanimod .05-mg and 1-mg compared with placebo in 197 patients with UC.

The primary endpoint was the number of patients who achieved remission after 8 weeks of therapy. Patients who achieved a clinical response by 8 weeks continued treatment through 32 weeks.

Previous findings showed improvements in the primary and secondary endpoints in patients treated with ozanimod 1-mg, according to Celgene.

Patients in all treatment arms were enrolled in the open-label extension if they did not respond to treatment after the initial 8 weeks, relapsed during maintenance therapy, or completed the maintenance phase. The objective of the extension was to investigate the long-term efficacy and safety of ozanimod 1-mg.

At week 93, 91% of patients had little to no disease activity. Additionally, 97% had little to no blood in their stool and 86% had no blood in their stool, according to the release.

In this study, the most common adverse events included UC flare, upper respiratory tract infection, and back pain.

"People with ulcerative colitis need additional treatment options that can provide long-term benefit," said William Sandborn, MD, professor of Medicine and chief, Division of Gastroenterology and director, University of California San Diego Inflammatory Bowel Disease Center. "These results further support the potential of longer-term treatment with ozanimod."