Zeposia maintains disease control even in the event of temporary treatment interruption for up to eight weeks

Zeposia is the first oral sphingosine 1-phosphate (S1P) receptor modulator approved to treat patients with ulcerative colitis

Bristol Myers Squibb (NYSE: BMY) today announced new post hoc analyses from the Phase 3 True North study evaluating the duration of response following continuous Zeposia (ozanimod) treatment for up to one year and following treatment interruption in patients with moderately to severely active ulcerative colitis (UC). After achieving a clinical response at the end of the induction period, 86.1% of patients who remained on Zeposia showed no disease relapse at Week 52 (Kaplan-Meier [KM] estimates of no disease relapse at Week 52: Zeposia/Zeposia, 86.1%; Zeposia/placebo, 62.6%).

As temporary treatment discontinuation may occur in clinical practice, these analyses evaluated the duration of response following treatment interruption. Findings showed that Zeposia maintained disease control for up to eight weeks in patients who switched to placebo after initial response (KM estimates of no disease relapse at Week 8: Zeposia/Zeposia, 96.1%; Zeposia/placebo, 90.6%). These analyses (Presentation #62) and 10 additional Zeposia abstracts demonstrating Bristol Myers Squibb’s robust body of research in gastroenterology are being presented at the American College of Gastroenterology (ACG) annual scientific meeting, taking place October 21 – 26, 2022.

"Understanding the duration of response after continuous ozanimod treatment is critical, as it can assist in clinical decision making when considering temporary discontinuation of UC treatment in clinical practice," said Bruce E. Sands, MD, MS, Gastroenterologist and paid consultant of Bristol Myers Squibb. Dr. Sands is also the Dr. Burrill B. Crohn Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai Health System. "These analyses reaffirm that ozanimod treatment is effective at helping patients remain relapse-free and suggest that a majority of patients remain relapse-free for up to eight weeks after treatment is interrupted.”

"These data presented at ACG demonstrate Zeposia treatment prevents disease relapse over one year of continuous treatment and maintains disease control even in the event of temporary interruption,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “These analyses reinforce the established profile of Zeposia for people living with moderately to severely active UC and underscore our long-standing commitment to the gastroenterology community.”

Additional analyses presented demonstrate no additional safety signals were observed after approximately two years of continuous Zeposia treatment.

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

Bristol Myers Squibb-sponsored abstracts featured at the ACG 2022 Scientific Meeting include:

• Duration of response to ozanimod after treatment withdrawal: Results from the Phase 3 True North study
  
  Author: Bruce E. Sands
  
  Presentation Number: 62
  
  Plenary Session 4A – Colon/IBD

• Efficacy and safety of 2 years of continuous ozanimod treatment: Interim analysis of the True North open-label extension study
  
  Author: Maria T. Abreu
  
  Presentation Number: D0406
  
  Poster

• Humoral immune responses to SARS-CoV-2 vaccines in an ozanimod open-label extension study
  
  Author: Freddy Caldera
  
  Presentation Number: E0367
  
  Poster

• Efficacy of ozanimod in vedolizumab-exposed patients with ulcerative colitis: A Phase 3 True North post hoc analysis
  
  Author: Bruce E. Sands
  
  Presentation Number: B0352
  
  Poster

Zeposia Clinical Encore Presentations

• Ozanimod is an effective oral treatment for patients with ulcerative colitis regardless of moderate or severe endoscopic disease activity at baseline: A post hoc analysis of the Phase 3 True North study
  
  Author: Douglas C. Wolf
  
  Presentation Number: C0387
  
  Poster

• Ozanimod is an effective oral treatment for patients with ulcerative colitis regardless of baseline endoscopic disease distribution: A post hoc analysis of the Phase 3 True North study
  
  Author: Anita Afzali
  
  Presentation Number: E0343
  
  Poster

• Evaluation of ozanimod efficacy and safety in older patients with ulcerative colitis: Post hoc analysis from the Phase 3 True North study
  
  Author: Nabeel Khan
  
  Presentation Number: A0391
  
  Poster

• Hepatic safety of ozanimod in ulcerative colitis and relapsing multiple sclerosis Phase 3 trials
  
  Author: David T. Rubin
  
  Presentation Number: B0368
  
  Poster

• Ozanimod is an efficacious oral therapy after 5-ASA failure in immunomodulator- and biologic-naive patients with ulcerative colitis: Post hoc analysis from True North
  
  Author: Bruce E. Sands
  
  Presentation Number: A0392
  
  Poster

• Association between absolute lymphocyte count and ozanimod efficacy/safety in patients with moderate/severe ulcerative colitis: Results from the Phase 3 True North study
  
  Author: Sarah Harris
  
  Presentation Number: E0354
  
  Poster

• Impact of ozanimod on fecal calprotectin levels and the association with efficacy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 True North study
  
  Author: Sarah Harris
  
  Presentation Number: E0355
  
  Poster

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 tumor necrosis factor (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 the maintenance study (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. 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.

For the True North open-label extension (OLE) study, eligible patients who completed the maintenance UC Study 2 were rolled into the OLE study, which is ongoing and designed to assess the longer-term profile of Zeposia for the treatment of moderately to severely active UC. Patients were also eligible to enter the OLE study if they completed UC Study 1 and did not achieve a clinical response or if they experienced a disease relapse during UC Study 2. 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 ulcerative colitis. More information about the open-label extension trial can be found on https://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 ulcerative colitis (UC) is unknown but may involve the reduction of lymphocyte migration into the intestines.

Bristol Myers Squibb is continuing to evaluate Zeposia in the ongoing True North open-label extension trial, 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 approved Zeposia for the treatment of adults with relapsing forms of multiple sclerosis in March 2020 and adults with moderately to severely active UC in May 2021. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis with active disease as defined by clinical or imaging features in May 2020 and for the treatment of adults with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent in November 2021.

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.

IMPORTANT SAFETY INFORMATION

Contraindications:

• Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a 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

• Patients taking a monoamine oxidase (MAO) inhibitor

Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA.

• Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.

• Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.

• In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.

• Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.

Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability.

PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.

If confirmed, treatment with ZEPOSIA should be discontinued.

Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:

• with significant QT prolongation

• with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs

• with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension

• with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block

Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease.

Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com.

Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA.

Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated.

Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued.

Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued.

Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended.

Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation.

Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA.

Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache.

Use in Specific Populations: Hepatic Impairment: Use is not recommended.

For additional safety information, please see the full Prescribing Information and 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 neurology. 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.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future post-marketing studies may not be consistent with the results of this study, that Zeposia, for the indication described in this release, may not be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such product candidate for such indication described in this release may be contingent upon verification and description of clinical benefit in additional confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2021, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

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$BMY announces Phase 3 results on the duration of response to an oral treatment for #ulcerativecolitis. #ACG2022