Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) approved Zeposia (ozanimod) 0.92 mg for the treatment of adults with moderately to severely active ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD).
Zeposia, an oral medication taken once daily, is the first and only sphingosine 1-phosphate (S1P) receptor modulator approved for patients with moderately to severely active UC. The mechanism by which Zeposia exerts therapeutic effects in UC is unknown but may involve the reduction of lymphocyte migration into the intestines. It is thought that by targeting S1P receptors on lymphocytes, a type of immune system cell, Zeposia reduces the number of lymphocytes in peripheral blood.
“Despite the availability of approved therapies, there is still unmet need and an opportunity to deliver additional treatment options to help patients better manages their disease,” said Adam Lenkowsky, general manager and head, US, Cardiovascular, Immunology and Oncology, Bristol Myers Squibb. “We’re thrilled that our pursuit of transformative science in immunology may benefit patients in their ulcerative colitis treatment by introducing a new option that has a different mechanism of action than available therapies. Zeposia combines disease control through lasting remission and demonstrated safety in a once-daily pill.”
The approval is based on data from True North, a pivotal phase 3 trial evaluating Zeposia as an induction and maintenance therapy versus placebo in adult patients with moderately to severely active UC. During induction at Week 10 (Zeposia N=429 versus placebo N=216) the trial met its primary endpoint of clinical remissiona (18% versus 6%, p<0.0001) as well as key secondary endpoints, including clinical responseb (48% versus 26%, p<0.0001), endoscopic improvementc (27% versus 12%, p<0.0001) and endoscopic-histologic mucosal improvementd (13% versus 4%, p<0.001) for Zeposia versus placebo, respectively. During maintenance at Week 52 (Zeposia N=230 versus placebo N=227) the trial met its primary endpoint of clinical remissiona (37% versus 19%, p<0.0001) as well as key secondary endpoints, including clinical response (60% versus 41%, p<0.0001), endoscopic improvement (46% versus 26%, p<0.001), corticosteroid-free clinical remissione (32% versus 17%, p<0.001) and endoscopic-histologic mucosal improvement (30% versus 14%, p<0.001) for Zeposia versus placebo, respectively. Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 2 (i.e., 1 week after completing the required 7-day dosage titration) in patients treated with Zeposia.
Zeposia is contraindicated in patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have the presence of Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase (MAO) inhibitor. Zeposia is associated with the following Warnings and Precautions: increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, posterior reversible encephalopathy syndrome (PRES), unintended additive immunosuppressive effects from prior immunosuppressive or immune-modulating drugs, and severe increase in disability and immune system effects after stopping Zeposia.
“In True North, Zeposia demonstrated efficacy for endpoints such as clinical remission, endoscopic and histological mucosal improvement and safety. All are very relevant considerations for patients with ulcerative colitis,” said Michael Chiorean, M.D., AGAF, FASGE, co-director of IBD Center, Swedish Medical Center, Seattle, Washington. “Zeposia has the potential to be an important new treatment option for adult patients with moderate to severe ulcerative colitis.”
“Ulcerative colitis can be debilitating and unpredictable for the people living with this chronic inflammatory bowel disease,” said Michael Osso, president & CEO of the Crohn’s & Colitis Foundation. “The approval of this new oral treatment is welcome news for our community and provides hope to many patients who are looking for new options to achieve symptom relief and remission.”
True North is a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of Zeposia (ozanimod) 0.92 mg in patients with moderately to severely active ulcerative colitis who had an inadequate response or were intolerant to any of the following: oral aminosalicylates, corticosteroids, immunomodulators or a biologic. Patients were to be receiving treatment with oral aminosalicylates and/or corticosteroids prior to and during the induction period. A total of 30% of patients had previously failed or were intolerant to TNF blockers. Of these patients, 63% received at least two biologics including TNF blockers. At study entry, mean age was 42 years, 60% were male and mean disease duration was 7 years; patient characteristics were well-balanced across treatment groups.9 In the 10 week induction study (UC Study 1), a total of 645 patients were randomized 2:1 to receive Zeposia (N=429) or placebo (N=216), of whom 94% and 89%, respectively, completed the induction study.
In maintenance (UC Study 2), a total of 457 patients who received Zeposia in either UC Study 1 or in an open-label arm and achieved clinical response at Week 10 were re-randomized 1:1 and were treated with either Zeposia 0.92 mg (N=230) or placebo (N=227) for 42 weeks, for a total of 52 weeks of treatment. Concomitant aminosalicylates were required to remain stable through Week 52.
Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia reduces the capacity of lymphocytes to migrate from lymphoid tissue, reducing the number of circulating lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the intestines.