New Zeposia (ozanimod) Data Highlight COVID-19 Outcomes and Preservation of Long-Term Cognitive Function from Separate Analyses in Patients with Relapsing Forms of Multiple Sclerosis

Rhea-AI Summary

Bristol Myers Squibb (NYSE: BMY) reported promising results from the Phase 3 DAYBREAK study concerning its drug Zeposia (ozanimod) for multiple sclerosis (MS). Over 90% of participants showed an immune response to COVID-19 vaccinations, all serious adverse events were absent. The study demonstrated that 68% of participants were relapse-free with an adjusted annualized relapse rate (ARR) of 0.099 after up to 74 months. These findings emphasize Zeposia's safety and efficacy, reinforcing its value in treatment options for MS.

Positive

• Over 90% immune response rate to COVID-19 vaccination in participants treated with Zeposia.
• 68% of participants in the DAYBREAK study reported being relapse-free.
• Adjusted annualized relapse rate (ARR) of 0.099 after up to 74 months of treatment.

Negative

• 88% of participants reported treatment-emergent adverse events (TEAEs) during the study.
• 14% of participants experienced serious TEAEs, raising concerns about long-term safety.

Retrospective analyses from the Phase 3 DAYBREAK open-label extension study showed more than 90% of participants who received Zeposia mounted a serologic response to COVID-19 vaccination

All adverse events related to COVID-19 in vaccinated study participants were nonserious

Data are among 13 abstracts being presented at ECTRIMS 2022 that further reinforce the safety and efficacy profile of Zeposia and Bristol Myers Squibb’s commitment to the multiple sclerosis community

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced new retrospective analyses on serologic responses and clinical outcomes with COVID-19 vaccination in participants treated with Zeposia (ozanimod) from the ongoing Phase 3 DAYBREAK open-label extension (OLE) study in relapsing multiple sclerosis (MS). More than 92% (137/148) of all study participants in these analyses mounted a serological response following vaccination. In addition, among participants with prior COVID-19 exposure, seroconversion was observed in 100% (39/39) of individuals following full COVID-19 mRNA or non-mRNA vaccination. COVID-19-related adverse events were reported in 10% (15/148) of vaccinated participants (12/148 confirmed; 3/148 suspected), all of which were nonserious.

The new analyses (Presentation #P1199) will be featured in the late-breaking research session on October 27, 2022, at the 38^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place in Amsterdam, the Netherlands.

“These data are of clinical importance for physicians treating multiple sclerosis, because they provide a greater understanding of how COVID-19 infections and vaccinations interplay with Zeposia treatment,” said Bruce Cree, MD, PhD, MAS, study investigator and professor of Clinical Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and Clinical Research Director, UCSF MS Center. “Regardless of prior COVID-19 exposure, most participants mounted an immune response following COVID-19 vaccination without experiencing adverse events, in contrast to some reports of other S1P modulators that described no response, adding insight to the treatment decision making process.”

Additional key Bristol Myers Squibb data presentations at ECTRIMS 2022 include:

• Interim analyses of the ongoing Phase 3 DAYBREAK OLE study showed that 68% of participants were relapse-free and demonstrated an adjusted annualized relapse rate (ARR) of 0.099 at up to 74 months of treatment. Findings also showed long-term efficacy was sustained on MRI measures after 60 months of treatment, with a mean number of new and enlarging T2 lesions per scan of 0.98, and on disability progression in up to 74 months of treatment, with a 6-month confirmed disability progression of 14%. Treatment emergent adverse events (TEAEs) were reported in 88% of participants, with 14% of participants reporting serious TEAEs; 3.6% of participants discontinued treatment due to TEAEs. (Presentation #P334; Author: Krzysztof Selmaj)

• Post hoc analyses of the Phase 3 SUNBEAM, RADIANCE and DAYBREAK OLE studies demonstrated that a greater proportion of patients treated with Zeposia versus interferon beta-1a had a lower annualized rate of brain volume loss (SUNBEAM study, Month 12: 50.9% versus 37.5%, respectively; RADIANCE study, Month 24: 63.1% versus 50%, respectively). In patients continuously treated with Zeposia, those with low annualized rate of brain volume loss (ARBVL) showed higher cognitive processing speed as measured by the mean symbol digits modalities test compared with those with high ARBVL (SUNBEAM study into OLE study, Month 60: 52.7 versus 45.4; RADIANCE study into OLE study, Month 72: 50.5 versus 40.5, respectively). (Author: Bruno Brochet; e-Poster #EP1082)

“We remain dedicated to pursuing pathbreaking science and collaborating with the scientific and patient communities to deepen our understanding on the use of our medicines and to help individuals with multiple sclerosis live healthier, more fulfilling lives,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “Our COVID-19 and disability progression findings, as well as our presentations demonstrating an association between Zeposia use and reduced brain volume loss along with improved cognitive processing speed, reinforce the importance of early intervention in the treatment of multiple sclerosis and Zeposia’s profile in the treatment armamentarium.”

Bristol Myers Squibb-sponsored abstracts featured at the ECTRIMS 2022 Congress:

• Serologic response and clinical outcomes of SARS-CoV-2 infection and vaccination in ozanimod-treated participants with relapsing multiple sclerosis
  Author: Bruce Cree
  Presentation number: P1199
  Session: Poster Session 2
  

• COVID-19 infections and vaccinations among patients receiving ozanimod in the DAYBREAK open-label extension trial
  Author: Bruce Cree
  Presentation number: P387
  Session: Poster Session 1
  

• Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Interim analysis of the DAYBREAK open-label extension study
  Author: Krzysztof Selmaj
  Presentation number: P334
  Session: Poster Session 1
  

• Correlations between early MRI parameters and long-term clinical outcomes in Phase 3 and open-label extension studies of ozanimod in relapsing multiple sclerosis
  Author: Douglas Arnold
  Presentation number: P358
  Session: Poster Session 1
  

• Proportion of relapsing MS patients with low vs high annualised whole brain volume atrophy rates after 5‒6 years of ozanimod and relationship to cognitive processing speed
  Author: Bruno Brochet
  e-Poster number: EP1082
  Session: e-Poster Session
  

• Impact of ozanimod on absolute lymphocyte count and recovery in patients with relapsing multiple sclerosis
  Author: Krzysztof Selmaj
  e-Poster number: EP1071
  Session: e-Poster Session
  

• Relationship between infections and absolute lymphocyte count during Phase 3 and open-label extension trials of ozanimod in patients with relapsing multiple sclerosis
  Author: Hans-Peter Hartung
  Presentation number: P707
  Session: Poster Session 2
  

• Safety patterns with ozanimod during Phase 3 and open-label extension trials in patients with relapsing multiple sclerosis
  Author: Krzysztof Selmaj
  Presentation number: P732
  Session: Poster Session 2
  

• NfL as a predictor of GdE lesions in patients with relapsing multiple sclerosis treated with ozanimod in the Phase 2 RADIANCE trial
  Author: Krzysztof Selmaj
  e-Poster number: EP1020
  Session: e-Poster Session
  

• Post hoc analysis of cognitive processing speed at time of first confirmed relapse in patients with relapsing multiple sclerosis treated with ozanimod vs interferon β-1A in the Phase 3 SUNBEAM trial
  ​Author: John DeLuca
  e-Poster number: EP1116
  Session: e-Poster Session
  

• Effect of disease modifying therapy on T2-flair-based neurodegenerative MRI outcomes: A longitudinal, real-world, US-based, multi-center multiple sclerosis study
  Author: Bruce Cree
  e-Poster number: EP1121
  Session: e-Poster Session
  

• The impact of cognitive impairment on disease burden in Chinese patients with multiple sclerosis: A model simulation study
  Author: Qian Jiang
  e-Poster number: EP0870
  Session: e-Poster Session
  

• Uncovering challenges in achieving health equity in multiple sclerosis care: A deep-dive into the experiences and perspectives of patients and their care teams in general neurology and MS specialty clinics
  Author: Mitzi Williams
  Presentation number: P110
  Session: Poster Session 1

Bristol Myers Squibb thanks the patients and investigators who are participating in our Zeposia clinical trials.

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 (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).

About RADIANCE

RADIANCE Part B was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral Zeposia (0.92 mg, equivalent to 1 mg) against weekly intramuscular AVONEX^® (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people living with relapsing forms of MS across 150 sites in 21 countries.

The primary endpoint of the trial was ARR over 24 months. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months.

About SUNBEAM

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 MS 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.

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, 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. 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 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 study results may not be consistent with the results to date, that any marketing approvals, if granted, may have significant limitations on their use, and that such product candidate for the indication described in this release, may not 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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FAQ

What were the results of the DAYBREAK study for BMY?

The DAYBREAK study showed that over 90% of participants mounted an immune response to COVID-19 vaccinations, with 68% being relapse-free and an adjusted annualized relapse rate (ARR) of 0.099.

How effective is Zeposia for multiple sclerosis according to the recent study?

The study indicated that Zeposia maintains long-term efficacy, with 68% of participants remaining relapse-free after up to 74 months.

What percentage of participants experienced serious adverse events in the DAYBREAK study?

In the DAYBREAK study, 14% of participants reported experiencing serious treatment-emergent adverse events.

What is the significance of the 90% immune response to COVID-19 for BMY?

A 90% immune response rate highlights Zeposia's compatibility with COVID-19 vaccinations, indicating its safety for patients with multiple sclerosis.