Bristol Myers Squibb (NYSE: BMY) today announced that ZEPOSIA® (ozanimod) 0.92 mg, a new once-daily oral medication for adults for the treatment of relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, is now commercially available in the U.S. ZEPOSIA was approved by the U.S. Food and Drug Administration (FDA) on March 25, 2020.1
*ZEPOSIA is the only approved sphingosine-1-phosphate (S1P) receptor modulator that offers appropriate RMS patients an initiation with no genetic test and no first dose observation.1,2,3 An up-titration scheme should be used to reach the maintenance dosage of ZEPOSIA, as a transient decrease in heart rate and atrioventricular conduction delays may occur.1 Before initiation of treatment with ZEPOSIA, all patients require assessments including a recent complete blood count including a lymphocyte count (within six months or after discontinuation of prior MS therapy), an ECG to determine whether preexisting conduction abnormalities are present, a recent liver function test (within six months), and consideration of current and prior medications, including vaccinations.1 For patients with a history of uveitis or macular edema, an ophthalmic assessment is required.1
“We are pleased to now bring ZEPOSIA, an important new once daily treatment option, to RMS patients,” said Tina Deignan, vice president and U.S. head of immunology, Bristol Myers Squibb. “ZEPOSIA is the first and only S1P that requires no first dose observation,1,2,3 which may minimize the number of interactions RMS patients need to have with healthcare practioners prior to initiating therapy during this unprecedented time of social distancing.”
ZEPOSIA is contraindicated in patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure; patients who have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase inhibitor.1 ZEPOSIA is associated with the following Warnings and Precautions: increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, posterior reversible encephalopathy syndrome, additive immunosuppressive effects from prior immune-modulating treatments, severe increase in disability after stopping ZEPOSIA, and immune system effects after stopping ZEPOSIA.1 Please see Important Safety Information for additional details.1 The most common adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.1
The ZEPOSIA 360 Support™ program will facilitate access to ZEPOSIA for appropriate patients with MS. This includes a co-pay of as little as $0 for eligible appropriate patients, assistance with financial support, reimbursement for some initial out-of-pocket medical costs – and a program that may help eligible patients with commercial insurance to receive free medication while they are waiting for insurance approvals. Terms, conditions, and eligibility criteria apply. More information is available at ZEPOSIA.com.
About Multiple Sclerosis
Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves.4 The myelin damage disrupts communication between the brain and the rest of the body.5 Ultimately, the nerves themselves may deteriorate — a process that's currently irreversible.6
RMS, including clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function.7 These attacks — often called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely with no apparent progression of disease.7 RMS is the most common disease course at the time of diagnosis.7 Approximately 85% of patients are initially diagnosed with RMS, compared with 10-15% with progressive forms of the disease.7
About ZEPOSIA® (ozanimod)
ZEPOSIA® is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5.1 ZEPOSIA blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.1 The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system.1
ZEPOSIA is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn's disease.8,9
ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
IMPORTANT SAFETY INFORMATION
Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker
Patients with severe untreated sleep apnea
Patients taking a monoamine oxidase (MAO) inhibitor
Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA
Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA
Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. No cases of PML were identified in active-controlled MS clinical trials with ZEPOSIA. PML has been reported in patients treated with S1P receptor modulators and other MS therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation. If confirmed, treatment with ZEPOSIA should be discontinued
In clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects
Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA
Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals:
with significant QT prolongation
with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
with a history of Mobitz type II second-degree or higher AV block, sick-sinus syndrome, or sinoatrial heart block
Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease
Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA
Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA
Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated
Macular edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued
Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued
Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended
Severe Increase in Disability After Stopping ZEPOSIA: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation
Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA
Most common Adverse Reactions (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
For additional safety information, please see the full Prescribing Information and Medication Guide.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether ZEPOSIA (ozanimod) for the indication described in this release will be commercially successful and that continued approval of ZEPOSIA for such indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
1 ZEPOSIA (ozanimod) capsules for oral use. Celgene Corporation. Full prescribing information. 3/2020.
2 GILENYA (fingolimod) capsules for oral use. Novartis Pharmaceuticals Corporation. Full prescribing information. 8/2019.
3 MAYZENT (siponimod) tablets for oral use. Novartis Pharmaceuticals Corporation. Full prescribing information. 3/2019.
4 National Multiple Sclerosis Society. Definition of MS. www.nationalmssociety.org/What-is-MS/Definition-of-MS. Accessed on April 15, 2020.
5 National Multiple Sclerosis Society. What is Myelin? www.nationalmssociety.org/What-is-MS/Definition-of-MS/Myelin. Accessed April 15, 2020.
6 National Multiple Sclerosis Society. What Causes MS? www.nationalmssociety.org/What-is-MS/What-Causes-MS. Accessed April 15, 2020.
7 National Multiple Sclerosis Society. Types of MS. www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed April 15, 2020.
8 Celgene. A Phase 3, Multicenter, Open-Label Extension Study of Oral Ozanimod for Moderately to Severely Active Crohn’s Disease. Available from www.clinicaltrials.gov/ct2/show/NCT03467958. NLM identifier: NCT03467958.
9 Celgene. To Evaluate Efficacy and Long-term Safety of Ozanimod in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis. Available from www.clinicaltrials.gov/ct2/show/NCT03915769. NLM identifier: NCT03915769.
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