Zeposia efficacious as induction, maintenance therapy for ulcerative colitis
Zeposia compared with placebo was more effective as an induction and maintenance therapy in patients with moderately to severely active ulcerative colitis, according to a study published in The New England Journal of Medicine.
“In a phase 3 clinical trial ozanimod was effective for induction and maintenance of clinical remission in patients with moderate to severe ulcerative colitis,” Jean-Frederic Colombel, MD, co-director of the Feinstein IBD Center at Mount Sinai and professor of medicine at the Icahn School of Medicine, told Healio Gastroenterology. “Importantly the drug was effective not only in in patients naïve of other therapies but also those previously exposed to biologic therapies. Despite recent progresses in the treatment of ulcerative colitis there is still unmet need for new effective oral therapies. Ozanimod is now a new alternative for our patients.”
Researchers performed a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of Zeposia (ozanimod, Bristol Myers Squibb) as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. During the 10-week induction period, 645 patients in cohort 1 received once daily oral ozanimod hydrochloride (n = 429) at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily (n = 216) in a double-blind manner. The 367 patients in cohort 2 received open-label ozanimod at the same daily dose. For the maintenance period through 52 weeks, 457 patients with a clinical response to ozanimod in either cohort were randomly assigned again to receive double-blind ozanimod or placebo.
The percentage of patients with clinical remission, evaluated with the three component Mayo score, served as the primary end point. Ranked, hierarchical testing was used to assess other clinical, endoscopic and histologic end points.
William J. Sandborn, MD, of the division of gastroenterology at the University of California, San Diego, and colleagues wrote, “The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6%; P < .001) and maintenance (37% vs. 18.5% [among patients with a response at week 10]; P < .001).”
Investigators noted the incidence of clinical response with ozanimod compared with placebo was higher during induction (47.8% vs. 25.9%; P < .001) and maintenance (60% vs. 41%; P < .001). In both periods all secondary endpoints improved significantly with ozanimod vs. placebo.
Serious infection occurred in less than 2% of patients in each group. With ozanimod, investigators noted more elevated liver aminotransferase levels.
“All primary and secondary endpoints were met including mucosal healing a composite of endoscopic and histological remission which has been associated with better long-term outcomes,” Colombel said.
Colombel said the long-term safety of ozanimod will be need be assessed in future studies.
“Next steps would be to determine the impact of ozanimod on modifying the natural history of ulcerative colitis and notably risk of colectomy and to learn how this drug should be best positioned in the treatment of ulcerative colitis,” Colombel said. “Cancer, opportunistic infections and macular edema were observed in patients treated with ozanimod but the events were rare.”
Editor's note: This article has been updated with quotes from a researcher.