Zeposia (ozanimod), an investigational anti-inflammatory medicine, significantly increased clinical remission and mucosal healing in patients with ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), Bristol Myers Squibb announced in a press release.
UC is an autoimmune disease characterized by an overproduction of lymphocytes — cells involved in the immune response — in the digestive system, also called the gastrointestinal (GI) tract. Consequently, symptoms such as inflammation, ulcers, and lesions start to appear and can affect patients’ quality of life at several levels.
Moreover, many individuals with UC show a poor response to currently available treatments, or don’t respond at all.
Zeposia is an investigational therapy that aims to reduce inflammation and allow the GI tract to heal, by adjusting the immune response. The treatment reduces the number of activated lymphocytes circulating in the GI tract by targeting two receptor proteins: the sphingosine-1-phosphate (S1P)-1 and -5.
The True North trial is a Phase 3, placebo-controlled study (NCT02435992) that was designed to evaluate the safety and efficacy of Zeposia (1 milligram) in the treatment of moderate to severe UC in people who did not adequately respond to prior treatment.
The primary goal is clinical remission, or the disappearance of all signs of the disease, as detected by a colonoscopy (endoscopic remission) and based on the Mayo endoscopic subscore (MES), an endoscopy-based scale.
Secondary endpoints include clinical response, endoscopic improvement, and mucosal healing. Mucosal healing was defined as endoscopic improvement with histologic remission — remission at the cell tissue level detected by a biopsy.
The study comprised two stages: the induction phase (up to week 10) and the maintenance phase, which continued until week 52, or the one-year mark.
In the induction phase, 645 patients with a mean age of 42 were randomly selected to receive Zeposia (429 patients) or a placebo (216 patients). These participants were divided into two treatment groups. In group 1, the patients were again randomly selected to receive the treatment or a placebo once daily for 10 weeks. Meanwhile, in group 2, a total of 367 patients were included in an open-label arm and were all treated once daily with Zeposia for 10 weeks.
In the maintenance phase, 457 patients were randomly assigned once again: 230 individuals were selected to receive Zeposia, while 227 were given a placebo. Treated participants from the induction phase who reached a clinical response at week 10 were randomly assigned a second time to receive either the treatment or a placebo until week 52. Patients on the placebo who achieved clinical response in the induction phase remained on the placebo during the maintenance phase.
The results showed that the study’s primary endpoints were achieved. At both phases, a meaningful clinical remission was observed in treated patients when compared with those receiving a placebo. Specifically, in the induction phase, 18.4% of the treated patients achieved meaningful clinical remission compared with 6.0% in the placebo group. In the maintenance phase, the remission rates were 37.0% for the treated group versus 18.5% among those receiving the placebo.
All secondary endpoints also showed statistically significant improvements at both phases of the study. A higher clinical response was observed in Zeposia-treated people compared with those receiving a placebo: 47.8% vs. 25.9% in the induction phase, and 60.0% vs. 41.0% in the maintenance phase.
“The data from the Zeposia True North trial demonstrate patients with moderate to severe ulcerative colitis achieved clinically meaningful improvements in key clinical, endoscopic and mucosal healing endpoints,” said William Sandborn, MD, director of the IBD Center at the University of California San Diego Health and a principal trial investigator.
“Notably, the endoscopic and histologic benefits, which can be difficult to achieve, suggest Zeposia has the potential to address the need for a safe and effective oral treatment option for this serious, chronic disease,” Sandborn added.
Regarding treatment-emergent adverse events (TEAEs), no new safety signals were observed. The most common TEAEs found in the induction period were anemia (4.2% in the Zeposia group vs. 5.6% in the placebo group), nasopharyngitis, a mild and common throat disease (3.5% vs. 1.4% with placebo), and headache (3.3% vs. 1.9% with placebo).
In the maintenance period, the most common TEAEs were an increase in the livers’ enzyme alanine aminotransferase (4.8% in the Zeposia group vs. 0.4% with placebo), and headache (3.5% vs. 0.4% with placebo).
Efficacy and safety results from the two phases of the study were presented at UEG Week Virtual 2020, recently held online.
“These Zeposia True North results represent a meaningful achievement for patients living with ulcerative colitis, many of whom have an inadequate response or do not respond at all to currently available therapies,” said Mary Beth Harler, MD, head of immunology and fibrosis development at Bristol Myers Squibb.
“We look forward to working with health authorities to bring Zeposia to this patient population and remain committed to pursuing new scientific advances to help deliver transformational medicines for the gastroenterology community,” Harler added.
Patients are now being enrolled in an open-label extension trial (NCT02531126) to evaluate the long-term safety and efficacy of Zeposia in people with moderate to severe UC who were treated with the therapy in previous trials.
Zeposia is already approved in the U.S. for the treatment of adults with relapsing multiple sclerosis. It also is being investigated for the treatment of active Crohn’s disease, another IBD, in the ongoing Phase 3 YELLOWSTONE clinical trial program (NCT03467958).