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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

 

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #BMS—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.

 

About DAYBREAK

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.

 

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 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

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 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

 

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 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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Analysis of ongoing DAYBREAK open-label extension trial of Zeposia showed that seroconversion occurred in 100% of those treated with mRNA vaccines and in a majority of those treated with non-mRNA vaccines

New analyses to be featured in late-breaking research session at the 8th European Academy of Neurology Congress in Vienna, Austria

Data are among five abstracts being presented that further reinforce the safety and efficacy profile of Zeposia

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #BMS—Bristol Myers Squibb (NYSE:BMY) today announced new data on COVID-19 vaccine responses in participants treated with Zeposia (ozanimod) from the ongoing Phase 3 DAYBREAK open-label extension (OLE) study in relapsing multiple sclerosis. For participants who showed no evidence of recent COVID-19 infection, results showed seroconversion occurred in 100% (80/80) and 62% (18/29) of fully vaccinated mRNA and non-mRNA vaccine recipients, respectively. These data are to be presented as late-breaking research (Presentation #OPR-162) on June 28, 2022 (8:45-9:00 CEST) at the European Academy of Neurology (EAN) Congress in Vienna, Austria.

This research was conducted from January 2020 to October 2021, and higher antibody levels were observed at all tested timepoints from four weeks to >12 weeks in mRNA vaccine recipients who completed the two-dose regimen (grand mean 512.6 U/mL, range: 1.3-4572) versus those with one dose (grand mean 39.3 U/mL, range: 0.4-368.5) indicating that patients on Zeposia develop an adequate primary response and may receive a potential benefit from booster doses.

 

“This study shows that all participants who received Zeposia as a treatment for multiple sclerosis were able to develop an immune response following mRNA vaccinations against COVID-19 infection,” 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. “Patients treated with Zeposia are much more likely to develop antibody responses to RNA vaccines compared to non-RNA vaccines. This observation may be helpful for physicians as they seek to optimize care for patients in the face of the ongoing COVID-19 pandemic.”

 

In a separate analysis of treatment-emergent COVID-19 events occurring from November 1, 2019 to May 10, 2021, results showed that the benefit:risk profile of Zeposia remains unchanged with most COVID-19 cases being non-serious, with the majority resolving without treatment interruption.

 

“We are committed to partnering with the research and medical communities to understand how our medicines should best be used in the context of the evolving COVID-19 pandemic,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “While more research is required, these data further confirm Zeposia’s consistent safety profile and demonstrate that individuals receiving Zeposia for multiple sclerosis mount a measurable antibody response to COVID-19 vaccination.”

 

Bristol Myers Squibb-sponsored abstracts that will be presented at the EAN Congress 2022 are listed below. Complete abstracts can be accessed online here.

 

Zeposia Presentations

• Serologic response to SARS-CoV-2 vaccines in DAYBREAK participants with relapsing multiple sclerosis receiving ozanimod

  Author: Bruce Cree

  Presentation number: OPR-162

  Session: Late-breaking news 2

• Positive association between baseline brain volume and long-term cognition in patients with relapsing multiple sclerosis

  Author: John DeLuca

  ePoster number: EPO-127

  Session: MS and related disorders 1

• Analysis of multiple sclerosis relapse following discontinuation of ozanimod in DAYBREAK

  Author: Ralf Gold

  ePoster number: EPO-131

  Session: MS and related disorders 1

• Efficacy of ozanimod in disease-modifying treatment naive vs experienced patients with relapsing multiple sclerosis

  Author: Hans-Peter Hartung

  ePoster number: EPR-050

  Session: MS and related disorders 1

• Long-term outcomes with ozanimod in the DAYBREAK extension trial by number of multiple sclerosis relapses during the Phase 3 trials

  Author: Patrick Vermersch

  ePoster number: EPR-160

  Session: MS and related disorders 3

 

Bristol Myers Squibb thanks the patients and investigators who are participating in the Phase 3 DAYBREAK OLE clinical trial.

 

About DAYBREAK

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.

 

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

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 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

 

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 and COVID-19. 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 regarding the spread and impact of COVID-19 and/or other 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. 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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In the pivotal Phase 3 TRANSFORM trial, single infusion of Breyanzi significantly outperformed the nearly 30-year standard of care with median event-free survival of 10.1 months vs. 2.3 months and a well-established safety profile

 

Approval was also based on data from the Phase 2 PILOT study, the first and only company-sponsored study of a CAR T cell therapy in patients with primary refractory or relapsed LBCL who are not considered candidates for transplant, in which Breyanzi delivered deep and durable responses

 

With this approval, Breyanzi now has the broadest patient eligibility of any CAR T cell therapy in relapsed or refractory LBCL, reinforcing company’s leadership in delivering innovative cancer treatments with Breyanzi as a cornerstone of its diversified cell therapy portfolio and pipeline

 

PRINCETON, N.J. — (BUSINESS WIRE) — $BMY #Breyanzi—Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has approved Breyanzi^® (lisocabtagene maraleucel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant (HSCT) due to comorbidities or age.

 

With these two new indications, Breyanzi now has the broadest patient eligibility of any CAR T cell therapy in relapsed or refractory LBCL. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome (CRS) and neurologic toxicities.

 

Breyanzi has demonstrated clinically meaningful and statistically significant improvements in event-free survival (EFS), complete responses (CR) and progression-free survival (PFS) compared to standard therapy in patients with LBCL that is primary refractory or relapsed within 12 months after first-line therapy. An improvement in EFS represents an increase in the length of time in which patients are alive and without disease progression or in need of further treatment. Breyanzi, a differentiated CAR T cell therapy, is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. Breyanzi can be administered in the inpatient or outpatient setting at a certified treatment center.

 

“As part of our commitment to developing innovative cancer treatments for patients with critical unmet need, Breyanzi offers a potentially curative option for more patients,” said Ester Banque, senior vice president & general manager, U.S. Hematology, Bristol Myers Squibb. “Based on the demonstrated clinical benefit, this approval of Breyanzi underscores the significant advances we are making to deliver on the promise of cell therapy.”

 

LBCL is a difficult-to-treat and aggressive blood cancer, and up to 40% of patients have disease that is refractory to or relapses after initial therapy. Historically, the only potential cure for these patients is the current standard of care consisting of intensive hospital-based salvage immunochemotherapy followed by high-dose chemotherapy and HSCT in those whose disease responds to the salvage therapy. However, half of patients are not considered candidates for a stem cell transplant due to age and/or comorbidities, and only an estimated 25% of those who are candidates are able to receive a stem cell transplant and experience long-term clinical benefit. For patients who are not considered candidates for stem cell transplant, treatment options are limited. If left untreated, relapsed or refractory LBCL has a life expectancy of just three to four months.

 

“Breyanzi represents a remarkable advance over a nearly 30-year standard of care, providing significantly improved efficacy with a well-established safety profile,” said Manali Kamdar, M.D., lead investigator of the TRANSFORM study and Associate Professor, Clinical Director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, University of Colorado Cancer Center. “This important milestone reinforces the benefit of offering a CAR T cell therapy option to patients earlier in their treatment journey and it’s critical that we begin the work to implement this therapy into standard practice as a second-line treatment in order to help improve outcomes for more patients.”

 

“Patients with large B-cell lymphoma whose disease does not respond to or relapses after first-line therapy often face lengthy and intensive cycles of chemotherapy with the goal of proceeding to stem cell transplant,” said Lee Greenberger, Ph.D., Chief Scientific Officer of the Leukemia & Lymphoma Society (LLS). “As one of the earliest supporters of CAR T since the 1990’s, LLS is excited to see the FDA approval of a CD19 CAR T cell therapy that has moved from later lines of therapy to a second-line option, which offers patients with relapsed or refractory large B-cell lymphoma the potential for long-term remission and the hope of a cure.”

 

Breyanzi is the only CAR T cell therapy that has been evaluated in a broad second-line patient population for LBCL in two distinct company-sponsored studies, including in patients whose disease relapsed within or later than 12 months following first-line treatment and regardless of transplant candidacy.

 

The approval of the expanded indications for Breyanzi is based on results from the pivotal Phase 3 TRANSFORM study in which adults with LBCL that was primary refractory or relapsed within 12 months of front-line therapy were randomized to receive Breyanzi or standard therapy consisting of salvage immunochemotherapy, and if responsive, high-dose chemotherapy and HSCT. The trial included patients with diverse histologic subtypes and high-risk features, and offered a patient-centric design, allowing for bridging immunochemotherapy in the Breyanzi arm for disease control, which reflects real-world clinical practice and allowed for inclusion of patients with more aggressive and fast-progressing disease. Due to the high rate of patients whose disease does not respond to salvage immunochemotherapy, the trial also allowed for crossover from the standard therapy arm to the Breyanzi arm if patients did not derive a response after three cycles of salvage chemotherapy or had disease progression at any time.

 

Results from the TRANSFORM study showed, Breyanzi (n=92) more than quadrupled median EFS compared to standard therapy (n=92) (10.1 months vs. 2.3 months [HR: 0.34; 95% CI (0.22-0.52) p<0.0001]). The majority of patients achieved a CR with Breyanzi compared to less than half with standard therapy (66% [95% CI: 56% – 76%] vs. 39% [95% CI: 29% – 50%]; p<0.0001), with median duration of CR not reached in the Breyanzi arm (95% CI: 7.9-NR). Results also showed Breyanzi more than doubled PFS versus standard therapy (median PFS: 14.8 months vs. 5.7 months [HR: 0.41; 95% CI: 0.25-0.66; p=0.0001]). In the study, nearly all patients (97%) in the Breyanzi arm received treatment versus less than half (47%) of patients who completed high-dose chemotherapy and autologous HSCT in the standard therapy arm.

 

The efficacy of Breyanzi in the second-line setting was also based on data from the Phase 2 PILOT study, in which 61 adults with primary refractory or relapsed LBCL who were not considered candidates for stem cell transplant were treated with Breyanzi. The PILOT study enrolled a broad patient population based on age, performance status and/or organ function and comorbidities, and regardless of time to relapse following first-line treatment. Breyanzi showed deep and durable responses, with an overall response rate of 80%, the study’s primary endpoint, and a CR rate of 54%, with median time to CR of one month (range: 0.8 – 6.9 months). Median duration of response was 11.2 months, with the median duration of response not reached for those patients who achieved a CR.

 

Breyanzi has a well-established safety profile and based on results from the TRANSFORM and PILOT studies, occurrences of CRS and neurologic events were generally low grade and mostly resolved quickly with standard protocols, and without the use of prophylactic steroids. Any-grade CRS was reported in less than half of patients (45%; 68/150), with Grade 3 CRS reported in 1.3% of patients. Any-grade neurologic events were reported in 27% (41/150) of patients treated with Breyanzi, with Grade 3 neurologic events reported in 7% of patients. Median time to onset of CRS was four days (range: 1 to 63 days) and median duration of CRS was four days (range: 1 to 16 days). The median time to onset of neurologic events was eight days (range: 1 to 63 days). The median duration of neurologic toxicities was six days (range: 1 to 119 days). The delayed onset of CRS and neurologic events allowed for the option of outpatient treatment and management of patients. In addition, the clinical profile of Breyanzi supported its use in a broad range of relapsed or refractory LBCL patients.

 

Breyanzi is broadly covered by commercial and government insurance programs in the U.S.

 

About Breyanzi

Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi was previously approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

 

Breyanzi is also approved in Europe, Switzerland, Canada and Japan for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma. For more information, visit clinicaltrials.gov.

 

About TRANSFORM

TRANSFORM (NCT03575351) is a pivotal, global, randomized, multicenter Phase 3 trial evaluating Breyanzi compared to current standard therapy regimens (platinum-based salvage chemotherapy followed by high-dose chemotherapy and HSCT in patients responding to salvage chemotherapy) in patients with large B-cell lymphoma that was primary refractory or relapsed within 12 months after CD20-antibody and anthracycline containing first-line therapy. Patients were randomized to receive Breyanzi or standard of care salvage therapy, including rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP), rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), or rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) per the investigators’ choice before proceeding to high-dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT). The primary endpoint of the study was event-free survival, defined as time from randomization to death from any cause, progressive disease, failure to achieve complete response or partial response, or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first. Complete response rate was a key secondary endpoint. Other efficacy endpoints included progression-free survival, overall survival, overall response rate and duration of response.

 

About PILOT

PILOT (NCT03483103) is a multicenter Phase 2 trial evaluating Breyanzi as a second-line therapy in adults with relapsed or refractory large B-cell lymphoma after front-line therapy who are not considered candidates for hematopoietic stem cell transplant (HSCT). All enrolled patients have relapsed or refractory large B-cell lymphoma after treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent. The primary endpoint of the study is overall response rate. Other efficacy endpoints include complete response rate, duration of response, progression-free survival, event-free survival and overall survival.

 

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
• Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
• BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

 

Cytokine Release Syndrome

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occur in 46% (190/418) of patients, including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.

 

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).

 

In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).

 

The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).

 

Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

 

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.

 

Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.

 

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.

 

In patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).

 

In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).

 

In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS.

 

The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).

 

CRS and Neurologic Toxicities Monitoring

Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.

 

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

 

• Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
• Certified healthcare facilities must have on-site, immediate access to tocilizumab.
• Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
• Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.

 

Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.

 

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

 

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion.

 

In patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.

 

Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

 

Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

 

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

 

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells.

 

In patients who received BREYANZI for LBCL, 15 of the 16 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.

 

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion.

Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL, and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.

Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.

 

In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% of patients.

 

Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

 

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

 

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

 

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.

 

Adverse Reactions

The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.

 

The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, hemoglobin decrease.

 

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

 

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility.

Contacts

Bristol Myers Squibb

Media Inquiries:
media@bms.com

Nikki Copas

nikki.copas@bms.com

Investors:
investor.relations@bms.com

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