PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE:BMY) today announced interim results from the Phase 3 open-label extension trial DAYBREAK, demonstrating the long-term efficacy and safety profile of Zeposia (ozanimod) in patients with relapsing forms of multiple sclerosis (MS). The trial included 2,494 patients who had previously completed a Phase 1, 2 or 3 Zeposia clinical trial and who had an average treatment time of 35.4 months while in DAYBREAK. These data (Presentation #P0217) will be presented at the MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting.
In the DAYBREAK extension study, no new safety concerns emerged with long-term use of Zeposia. At months 24 and 36, 79% and 75% of participants, respectively, were relapse-free and 3- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of participants in the trial, respectively. The average number of new/enlarging T2 lesions per scan at 24 months was similar, regardless of parent-trial treatment group (RADIANCE, SUNBEAM and RPC01-1001 clinical studies), as were the average number of gadolinium-enhanced (GdE) lesions at month 24.
“Gaining insight into long-term therapeutic outcomes can enable clinicians to identify the most appropriate treatment approach for their multiple sclerosis patients. The DAYBREAK trial provides us with important context regarding the longer-term efficacy and safety profile of Zeposia,” said Bruce Cree, M.D., Ph.D., M.A.S., study investigator and Professor of Clinical Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and clinical research director, UCSF MS Center.
In the DAYBREAK trial, of 2,494 participants exposed to Zeposia for a total of 35.4 months, 2,039 participants (81.8%) had any treatment-emergent adverse event (TEAE), 236 (9.5%) had a serious TEAE (SAE) and 56 (2.2%) discontinued the study due to a TEAE. The most common TEAEs were nasopharyngitis (17.9%), headache (14%), upper respiratory tract infection (9.9%) and lymphopenia (9.6%). There have been no serious opportunistic infections and exposure-adjusted incidence rates of TEAEs and SAEs have decreased over time.
“At MSVirtual2020, we’re excited to share new findings from DAYBREAK as well as a breadth of studies accelerating our understanding of relapsing forms of multiple sclerosis and adding to our growing body of knowledge of Zeposia,” said Mary Beth Harler, M.D., head of Immunology and Fibrosis Development, Bristol Myers Squibb. “Alongside our industry-leading collaborators, we are investigating novel endpoints, brain volume and cognition, which may help to further our understanding of the safety and efficacy profile of Zeposia and can advance transformational science for multiple sclerosis patients experiencing this unpredictable, debilitating disease.”
At the MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting, Bristol Myers Squibb and collaborators will present 15 clinical and non-clinical abstracts that reinforce the breadth and depth of the company’s research in MS. Abstracts include company-sponsored and collaborative studies with academic partners such as Brigham and Women’s Hospital and Cleveland Clinic. Accepted regular abstracts are available on the MSVirtual2020 online meeting library.
Summary of Presentations:
Bristol Myers Squibb studies featured at the MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting include:
Studies Evaluating Long-Term Safety Profile of Zeposia
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Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis in DAYBREAK: an open-label extension study of ozanimod phase 1−3 trials
Author: Selmaj
Presentation Number: P0217
Presentation Topic: Clinical Trials
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Pregnancy outcomes in the ozanimod multiple sclerosis clinical development program
Author: Minton
Presentation Number: P1133
Presentation Topic: Reproductive Aspects and Pregnancy
Studies Evaluating Zeposia Benefit to Risk Profile
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Inhibition of drug transporter breast cancer resistance protein has no effect on the pharmacokinetics of major active metabolites of ozanimod
Author: Zhang
Presentation Number: P0343
Presentation Topic: Disease Modifying Therapies – Risk Management
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Effect of ozanimod on proportions of leukocyte subsets in patients with relapsing multiple sclerosis
Author: Harris
Presentation Number: P0325
Presentation Topic: Disease Modifying Therapies – Mechanism of Action
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Post-treatment recovery of lymphocyte subsets in healthy volunteers treated with ozanimod
Author: Harris
Presentation Number: P0228
Presentation Topic: Clinical Trials
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Species variation in sphingosine 1-phosphate receptor subtype 5 affects response to ozanimod in preclinical models of multiple sclerosis
Author: Selkirk
Presentation Number: P0395
Presentation Topic: Disease Modifying Therapies – Mechanism of Action
Studies Evaluating Zeposia as an Oral Treatment Option for RMS
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Treatment discontinuation and restart among patients with multiple sclerosis using disease-modifying therapies
Author: Fox
Presentation Number: P0927
Presentation Topic: Observational Studies
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Comparative effectiveness of ozanimod versus dimethyl fumarate: results of a matching-adjusted indirect comparison
Author: Cohan
Presentation Number: P0046
Presentation Topic: Clinical Outcome Measures
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Comparative efficacy and safety of ozanimod versus teriflunomide for relapsing-remitting multiple sclerosis: a matching-adjusted indirect comparison
Author: Cohan
Presentation Number: P0047
Presentation Topic: Clinical Outcome Measures
Studies Evaluating Novel Endpoints in Monitoring MS Disease Progression
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Neurofilament light chain concentration predicts risk of relapse in participants with relapsing multiple sclerosis in phase 3 ozanimod trials
Author: Harris
Presentation Number: P0118
Presentation Topic: Biomarkers and Bioinformatics
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Comparison of models for disability accumulation on the expanded disability status scale in multiple sclerosis
Author: Healy
Presentation Number: P1010
Presentation Topic: Patient-Reported Outcomes and Quality of Life
Studies Exploring Brain Volume and Cognition in MS
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Understanding the patient and clinician perspective of ideal treatments for multiple sclerosis via group concept mapping
Author: Singer
Presentation Number: P1067
Presentation Topic: Patient-Reported Outcomes and Quality of Life
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Brain volume loss is an important treatment attribute among RRMS patients: findings from a discrete choice experiment
Author: Beusterien
Presentation Number: P1008
Presentation Topic: Patient-Reported Outcomes and Quality of Life
About DAYBREAK
DAYBREAK is a Phase 3, multi-center, long-term open-label extension (OLE), randomized, double-blind, double-dummy, active-controlled, parallel group study to evaluate the safety and efficacy of Zeposia (ozanimod) administered orally to patients with relapsing forms of multiple sclerosis (RMS).
Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with RMS are enrolled to receive treatment until the end of the DAYBREAK (approximately 7 years) or until the development program is discontinued. Patients in the trial are receiving Zeposia 0.92 mg (equivalent to ozanimod HCl 1 mg). In total, 2,639 participants completed the parent clinical trials, and this interim analysis (data cutoff December 20, 2019), includes a total of 2,494 participants with mean (range) Zeposia exposure of 35.4 (0.03–50.2) months in the OLE.
The primary objective of the trial was to evaluate safety in the overall population.
About Multiple Sclerosis
Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate — a process that's currently irreversible. MS affects 700,000 people in Europe and approximately 2.5 million people worldwide.
RMS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function. These attacks — often called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely with no apparent progression of disease. RMS is the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with RMS, compared with 10-15% with progressive forms of the disease.
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 blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system.
The U.S. Food and Drug Administration (FDA) approved Zeposia 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. Zeposia is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn's disease.
U.S. FDA-APPROVED INDICATION FOR ZEPOSIA
ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, 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 or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, 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 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.
- Progressive Multifocal Leukoencephalopathy (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. No cases of PML were identified in active-controlled MS clinical trials with ZEPOSIA. PML has been reported in patients treated with S1P receptor modulators and other MS 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
- In 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. 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
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 sinoatrial 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
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 Disability After Stopping ZEPOSIA: 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 (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
For additional safety information, please see the full Prescribing Information and Medication Guide.
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.
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 historical performance and 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 study results will be consistent with the results to date. 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, 2019, 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.
