PRINCETON, N.J.- Bristol Myers Squibb (NYSE:BMY) today announced that the U.S. 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).¹ 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.^1,3,4

“Despite the availability of approved therapies, there is still unmet need and an opportunity to deliver additional treatment options to help patients better manage their disease,” said Adam Lenkowsky, general manager and head, U.S., Cardiovascular, Immunology and Oncology, Bristol Myers Squibb.⁵ “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.”¹

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 remission^a (18% versus 6%, p<0.0001) as well as key secondary endpoints, including clinical response^b (48% versus 26%, p<0.0001), endoscopic improvement^c (27% versus 12%, p<0.0001) and endoscopic-histologic mucosal improvement^d (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 remission^a (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 remission^e (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. Please see Important Safety Information for additional details. The most common adverse reactions (incidence ≥ 4%) were liver test increased, upper respiratory infection, and headache.¹

“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.⁶ “Zeposia has the potential to be an important new treatment option for adult patients with moderate to severe ulcerative colitis.”¹

“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.^2,7,8 “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.”¹

Bristol Myers Squibb is committed to making Zeposia accessible to the patients who need it. The Zeposia 360 Support™ program will facilitate access to Zeposia for appropriate patients with UC. This includes a co-pay program for eligible appropriate patients to pay as little as $0 for their Zeposia prescription, assistance with financial support and a program that may help eligible patients with commercial insurance to receive free medication while they are experiencing delays or issues with insurance coverage. Support for eligible patients is also available for the routine initiation assessments, such as lab work. Through the program, health care professionals can opt to have eligible patients receive these tests in their own homes. These costs, whether incurred at home or in office, may be reimbursed. Terms, conditions, and eligibility criteria apply. More information is available at Zeposia.com.

A Marketing Authorization Application for Zeposia for the treatment of adults with moderately to severely active UC in the European Union is currently under review with the European Medicines Agency (EMA). A regulatory decision from the EMA is expected the second half of 2021.

About True North
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.¹ 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.⁹

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.¹ Concomitant aminosalicylates were required to remain stable through Week 52. Patients on concomitant corticosteroids were to taper their dose upon entering the maintenance study.¹ Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study.¹⁰

All eligible patients were rolled into an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis.¹⁰ More information can be found on www.clinicaltrials.gov, NCT02435992.

About Ulcerative Colitis
Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), is characterized by an irregular, chronic immune response that creates inflammation and ulcers (sores) in the mucosa (lining) of the large intestine (colon) or rectum.⁶ Symptoms include bloody stools, severe diarrhea and frequent abdominal pain.¹¹ Ulcerative colitis has a major impact on patients' health-related quality of life, including physical functioning, social and emotional well-being and ability to go to work/school.⁶ Many patients have an inadequate response or do not respond at all to currently available therapies.⁵ As of 2015, it was estimated that approximately 3 million adults in the United States have IBD, which includes UC and Crohn's disease.¹²

About Zeposia^® (ozanimod)
Zeposia^® (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5.^1,4Zeposia reduces the capacity of lymphocytes to migrate from lymphoid tissue, reducing the number of circulating lymphocytes in peripheral blood.⁴ The mechanism by which Zeposia exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the intestines.

Bristol Myers Squibb is continuing to evaluate Zeposia in an open-label extension trial, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active ulcerative colitis. The company is also investigating Zeposia for the treatment of moderately to severely active Crohn’s disease in the ongoing Phase 3 YELLOWSTONE clinical trial program.

Zeposia was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features in May 2020. The European Medicines Agency (EMA) validated Bristol Myers Squibb’s Marketing Authorization Application for Zeposia for the treatment of adults with moderately to severely active ulcerative colitis in December 2020. A regulatory decision from the EMA is expected in the second half of 2021.