Bristol Myers Squibb Receives European Commission Approval of Zeposia (ozanimod) for use in Adults with Moderately to Severely Active Ulcerative Colitis

Zeposia brings a new way of treating this chronic immune-mediated disease, approved for adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent

Zeposia is the first and only oral sphingosine 1-phosphate (S1P) receptor modulator for UC, with this approval marking its second indication in the European Union

Zeposia approval is based on the Phase 3 True North trial, which demonstrated clinically meaningful improvements in key clinical, endoscopic and mucosal healing endpoints, with no new safety signals observed

PRINCETON, NJ, USA I November 23, 2021 IBristol Myers Squibb (NYSE:BMY) today announced the European Commission has granted a Marketing Authorization for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. Zeposia, an oral medication taken once daily, is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P subtypes 1 (S1P1) and 5 (S1P5). Zeposia is the first and only oral S1P receptor modulator approved for UC, and represents a new way of treating this chronic immune-mediated disease.

“With today’s European Commission approval of Zeposia for ulcerative colitis, patients and physicians now have a once-daily oral treatment option to help address this debilitating disease, with a demonstrated efficacy and safety profile and a different mechanism of action than other available therapies,” said Jonathan Sadeh, M.D., MSc., senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “We are proud of our heritage in transformational science and innovative medicines that has brought us to this stage and look forward to offering appropriate patients in Europe a new therapy that provides significant symptom relief and lasting clinical remission.”

The approval was 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. Key findings from the trial include:

  • 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.
  • In the induction and maintenance phases of the True North trial, the overall safety profile was consistent with the known safety profile for Zeposia and patients with moderate to severe UC.

“The findings from the True North trial show that Zeposia demonstrated significant, durable efficacy in patients with moderate to severe ulcerative colitis across multiple key endpoints such as clinical improvement, endoscopic and mucosal healing and clinical remission,” said Dr. Silvio Danese, M.D., Director, Gastroenterology and Endoscopy, IRCCS, San Raffaele Hospital and University Vita-Salute San Raffaele in Milan. “The results for endoscopic improvement and histologic remission are particularly meaningful because they can be very difficult to achieve, indicating that Zeposia has the potential to be an effective and safe oral treatment option for clinicians treating adults living with this serious, chronic disease.”

“In Europe, over 3 million people are affected by inflammatory bowel disease, which includes ulcerative colitis, a challenging and often debilitating form of the disease,” said Luisa Avedano, CEO, European Federation of Crohn's & Ulcerative Colitis Associations. “I’m thrilled that we now have a new treatment option for patients and their caregivers as they manage the symptoms of a disease that can have a such detrimental impact on quality of life.”

Zeposia is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, as listed in the Summary of Product Characteristics (SmPC); immunodeficient state; patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization or New York Heart Association (NYHA) Class III/IV heart failure; patients with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker; severe active infections, active chronic infections such as hepatitis and tuberculosis; active malignancies; severe hepatic impairment (Child-Pugh class C); and during pregnancy and in women of childbearing potential not using effective contraception. The most commonly reported adverse reactions (>5%) in controlled periods of the adult multiple sclerosis (MS) and UC clinical studies are nasopharyngitis, alanine aminotransferase (ALT) increased, and gamma-glutamyl transferase (GGT) increased. The most common adverse reactions leading to discontinuation were related to liver enzyme elevations (1.1%) in the MS clinical studies. Liver enzyme elevations leading to discontinuation occurred in 0.4% of patients, in UC controlled clinical studies. The overall safety profile was similar for patients with MS and UC.

Bristol Myers Squibb thanks the patients and investigators involved in the True North clinical trial.

About True North

True North is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of Zeposia 0.92 mg in patients with moderately to severely active ulcerative colitis (UC) 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. 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. No new safety signals were observed in the induction phase.

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 (UC Study 2), for a total of 52 weeks of treatment. Concomitant aminosalicylates were required to remain stable through week 52. Patients on concomitant corticosteroids were to taper their dose upon entering the maintenance study. Of these, 80% and 54.6% of patients who received Zeposia and placebo, respectively, completed the study. In the maintenance phase, the overall safety profile was consistent with the known safety profile for Zeposia and patients with moderate to severe UC. More information about the True North trial can be found on www.clinicaltrials.gov, NCT02435992.

The clinical findings from True North, entitled “Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis,” were published in the September 30th issue of The New England Journal of Medicine.

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 UC. Among patients who entered the trial clinical remission, clinical response, endoscopic improvement, and symptomatic remission were generally maintained through week 142. No new safety concerns were identified in this study extension in patients with UC. More information about the open-label extension trial can be found on www.clinicaltrials.gov, NCT02531126.

About Ulcerative Colitis

Ulcerative colitis, 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. Symptoms include bloody stools, severe diarrhea and frequent abdominal pain. 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. Many patients have an inadequate response or do not respond at all to currently available therapies. It is estimated that approximately 12.6 million people worldwide are living with IBD.

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. 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 UC 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 UC. 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.

The U.S. Food and Drug Administration (FDA) approved Zeposia for the treatment of adults with moderately to severely active UC on May 27, 2021, and 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.

U.S. FDA APPROVED INDICATIONS

ZEPOSIA (ozanimod) is indicated for the treatment of:

1. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

2. Moderately to severely active ulcerative colitis (UC) in adults.

For additional safety information, please see the full Prescribing Informationand Medication Guide.

Bristol Myers Squibb: Pioneering Paths Forward in Immunology to Transform Patients’ Lives

Bristol Myers Squibb is inspired by a single vision – transforming patients’ lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can take a toll on their physical, emotional and social well-being, making simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, and our passion to help patients, the company continues to pursue pathbreaking science with the goal of delivering meaningful solutions that address unmet needs in rheumatology, gastroenterology, dermatology and multiple sclerosis. We follow the science, aiming to tailor therapies to individual needs, improve outcomes and expand treatment options by working to identify mechanisms with the potential to achieve long-term remission – and perhaps even cures – in the future. By building partnerships with researchers, patients and caregivers to deliver innovative treatments, Bristol Myers Squibb strives to elevate patient care to new standards and deliver what matters most – the promise of living a better life.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

a Clinical remission is defined as: rectal bleeding subscore = 0, stool frequency subscore = 0 or 1 (and a decrease from baseline in the stool frequency subscore of ≥ 1 point), and endoscopy subscore = 0 or 1 without friability.
b Clinical response is defined as a reduction from baseline in the 3-component Mayo score of ≥ 2 points and ≥ 35%, and a reduction from baseline in the rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1.
c Endoscopic improvement is defined as a Mayo endoscopy subscore of 0 or 1 without friability.
d Endoscopic-histologic mucosal improvement is defined as both Mayo endoscopic subscore of 0 or 1 without friability and histologic improvement of colonic tissue (defined as no neutrophils in the epithelial crypts or lamina propria and no increase in eosinophils, no crypt destruction, and no erosions, ulcerations, or granulation tissue, i.e., Geboes <2.0).
e Corticosteroid-free remission is defined as clinical remission at Week 52 while off corticosteroids for ≥ 12 weeks.

SOURCE: Bristol Myers Squibb

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