Celgene recently presented positive data from two Phase 2 studies — the STEPSTONE and TOUCHSTONE studies — for the company’s investigational compound ozanimod (RPC-1063) as a therapy for Crohn’s disease and ulcerative colitis at the World Congress of Gastroenterology at ACG2017 in Orlando, Florida, Oct. 13-18.
“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,” Terrie Curran, president of Celgene Inflammation and Immunology, said in a press release. “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 ongoing, open-label STEPSTONE study (NCT02531113) enrolled patients with moderately to severely active Crohn’s disease and has two periods — induction and extension. Patients are first enrolled in an induction period of 12 weeks, where they all receive 1.0 mg of ozanimod daily. Patients who complete the induction period may then be eligible to enter the 100-week extension period where they will continue to receive study medication.
Celgene presented the data for the induction period that included 69 patients (with a mean age of 37.7 years) with moderately to severely active Crohn’s disease.
Following the 12-week treatment period, researchers detected that the simple endoscopic score for Crohn’s disease (SES-CD) was reduced by more than 50% and 25% in 27% and 43% of patients, respectively.
The endoscopy improvements were particularly noticeable in patients with shorter disease duration (five years or less) and in patients with lower baseline endoscopic disease activity.
The analysis of Crohn’s disease activity index (CDAI) was performed on 59 patients. At week 12, a CDAI decrease of over 100 was detected in 66% of patients, and CDAI remission (corresponding to a score below 150) was observed in 46% of patients.
“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 in Canada. “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.”
In the TOUCHSTONE study (NCT01647516), an open-label extension study, researchers evaluated both the effectiveness and safety of two different doses of ozanimod — 0.5 mg and 1.0 mg — compared with a placebo control after eight weeks of treatment (the induction phase).
In total, the study enrolled 197 patients with moderate to severe ulcerative colitis. The study’s primary endpoint was to assess those who achieved remission after the induction period. Those who achieved a clinical response by week 8 proceeded to the maintenance phase in which patients received the same dose for up to 32 weeks.
Patients treated with the 1 mg dose of ozanimod achieved significant improvements when compared to placebo controls.
Patients in all of the study groups (0.5 mg dose, 1.0 mg dose, and placebo) who failed to respond to treatment after the induction phase, relapsed during the maintenance phase, or completed the maintenance phase were allowed to move to the open-label extension phase. Of 197 patients, 170 joined the extension phase, which aimed to assess the long-term (92 weeks) effectiveness and safety of daily ozanimod when administered as a 1.0 mg dose.
The analysis showed that out of 100 patients, 91% showed little or no active disease, as denoted by the physician global assessment (PGA 0 or 1) score. Additionally, 97% had little or no blood in their stools (rectal bleeding subscore, RBS, 0 or 1), and 86% were negative for bloody stools altogether (RBS 0).
At week 92, there was no difference in safety profile between the placebo group and ozanimod-treated patients.
“People with ulcerative colitis need additional treatment options that can provide long-term benefit,” said William Sandborn, MD, professor of medicine, chief of the division of gastroenterology, and director of the University of California at San Diego’s Inflammatory Bowel Disease Center. “These results further support the potential of longer-term treatment with ozanimod.”