Results showed improved or preserved cognitive function in a majority of people regardless of baseline values, with the greatest effect observed in almost 80% of people with high thalamic volume (45.5% improved and 34.1% preserved) at Month 48 of the DAYBREAK open-label extension trial
Zeposia was well tolerated, with more than 80% of people staying on therapy through 48 months
New analyses to be presented at the 8th European Academy of Neurology Congress in Vienna, Austria
Bristol Myers Squibb (NYSE:BMY) today announced new post-hoc analyses from the Zeposia (ozanimod) Phase 3 DAYBREAK open-label extension (OLE) and Phase 3 SUNBEAM trials, showing early Zeposia use demonstrated cognitive benefits in people with relapsing multiple sclerosis (MS), with the greatest effect seen in people with high thalamic volume (TV), supporting an association between preserved brain volume (BV) and improved long-term cognitive outcomes. These data (Presentation #EPO-127) are being presented at the European Academy of Neurology (EAN) Congress taking place in Vienna, Austria, from June 25-28.
"Multiple sclerosis can lead to significant, irreversible brain volume loss and decreased cognition if not treated quickly upon diagnosis. These new analyses show the potential of early treatment with Zeposia to help stabilize and even improve cognition in people with multiple sclerosis with high brain volume, which is important for doctors and people with multiple sclerosis," said John DeLuca, PhD, senior vice president for research and training, Kessler Foundation, and professor, Department of Physical Medicine & Rehabilitation and of Neurology, Rutgers New Jersey Medical School.
In these new exploratory analyses, Zeposia treatment showed improved or preserved cognitive function in a majority of patients, with the greatest improvement seen when used early in the disease when TV remains high, supporting a positive association between preserved BV and long-term cognitive performance. Zeposia was well tolerated with more than 80% of people who started the Phase 3 SUNBEAM trial (N=399 at baseline) remaining on continuous therapy through 48 months of the Phase 3 DAYBREAK OLE study (N=326).
Findings from the new research showed that people with high versus low BV, particularly TV, had higher cognitive performance, as assessed by the symbol digit modalities test (SDMT) score, at baseline. This trend remained stable or improved over 4-5 years of Zeposia treatment, leading to improved or preserved cognitive function in almost 80% of people with high TV (SDMT improved: 45.1%; SDMT preserved: 34.4%) and approximately 66% of people with low BV (SDMT improved: 35.6%; SDMT preserved: 30.7%) at Month 48 of the Phase 3 DAYBREAK OLE study.
"At Bristol Myers Squibb, we're committed to pathbreaking science in multiple immune-mediated diseases with the goal of alleviating the symptoms and disease progression experienced by individuals suffering from these illnesses and, ultimately, elevating the standard of care," said Jonathan Sadeh , MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. "We're excited by the potential effect of Zeposia in protecting cognitive function when used early in treatment before brain volume is lost and what it can mean for individuals with relapsing multiple sclerosis."
Bristol Myers Squibb thanks the patients and investigators involved in the Phase 3 DAYBREAK OLE and Phase 3 SUNBEAM clinical trials.
DAYBREAK is a Phase 3, multicenter, 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 (MS).
Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with relapsing forms of MS are enrolled to receive treatment until the end of the DAYBREAK trial 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 February 2021) includes a total of 2,494 participants with mean (range) Zeposia exposure of 46.8 (0.03-62.7) months in the OLE study.
SUNBEAM was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral Zeposia (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCl, respectively) against weekly intramuscular AVONEX ® (interferon beta-1a) for at least a 12-month treatment period. The study included 1,346 people living with relapsing forms of multiple sclerosis (RMS) across 152 sites in 20 countries.
The primary endpoint of the trial was annualized relapse rates during the treatment period. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months, number of gadolinium-enhanced brain MRI lesions at Month 12 and percent change from baseline in whole brain volume at Month 12. Cortical grey and thalamic volume changes were also prospectively assessed versus active comparator.
An analysis of the time to onset of three-month confirmed disability progression was prespecified using pooled data from both the SUNBEAM and RADIANCE Part B Phase 3 trials.
About Multiple Sclerosis
Multiple sclerosis (MS) is a disabling, unpredictable 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.
Relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease and active secondary progressive disease, are 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. During these recovery periods, also called remissions, symptoms improve partially or completely with no apparent progression of disease. Since MS relapses are unpredictable, patients can feel frustrated, stressed or scared when they occur. Relapsing forms of MS are the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with relapsing forms of MS, 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 (MS) is unknown but may involve the reduction of lymphocyte migration into the central nervous system.
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 and 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 in November 2021. The U.S. Food and Drug Administration (FDA) approved Zeposia for the treatment of adults with relapsing forms of MS in March 2020 and for adults with moderately to severely active UC on May 27, 2021.
U.S. FDA-APPROVED INDICATIONS FOR ZEPOSIA
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
- 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 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
- 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
- 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. PML has been reported in patients treated with S1P receptor modulators 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
- 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
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
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 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
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 study results may not be consistent with the results to date, that Zeposia (ozanimod) may not receive regulatory approval for the additional indication described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such additional indication described in this release will be commercially successful. 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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