Bristol Myers Squibb Receives European Commission Approval for Zeposia (ozanimod) for the Treatment of Adult Patients with Relapsing Remitting Multiple Sclerosis with Active Disease

Zeposia offers relapsing remitting multiple sclerosis (RRMS) patients with active disease in the European Union a new oral option to help address the disease’s hallmark relapses and brain lesions

Zeposia is the only approved sphingosine-1-phosphate (S1P) receptor modulator for RRMS patients with active disease

Zeposia adds to Bristol Myers Squibb’s immunology franchise and marks the first European Commission marketing authorization since the Celgene acquisition

(PRINCETON, N.J., May 27, 2020) – Bristol Myers Squibb (NYSE:BMY) today announced that the European Commission (EC) has approved Zeposia (ozanimod) for the treatment of adult patients with relapsing remitting multiple sclerosis (RRMS) with active disease as defined by clinical or imaging features. With the EC marketing authorization, Zeposia, an oral medication taken once daily, becomes the only approved sphingosine-1-phosphate (S1P) receptor modulator for RRMS patients with active disease. The approval is based on data from the SUNBEAM™ and RADIANCE™ Part B clinical trials showing that, as compared to AVONEX® (interferon beta-1a), Zeposia delivered powerful efficacy as measured by annualized relapse rate (ARR), as well as on the number and size of brain lesions.

“Today’s European Commission approval provides the opportunity for patients with RRMS with active disease to be offered Zeposia as a new first-line treatment option, which is an important advancement based on Phase 3 trial results showing significant improvements in relapses and brain lesions caused by this devastating disease,” said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb. “We share this achievement with the courageous multiple sclerosis patient community in Europe and around the globe, and are working closely with all stakeholders to ensure that eligible European patients can start benefitting from Zeposia as quickly as possible.”

Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves, creating damaging lesions that make it harder for signals to travel between each nerve cell. This “signal breakdown” can lead to symptoms and relapses.

The approval was based on data from the randomized, active-controlled Phase 3 SUNBEAM and RADIANCE Part B clinical trials, which enrolled more than 2,600 patients across 150 sites in more than 20 countries. Key findings from the trials include:

“There is no one-size-fits-all approach to treating MS. Patients respond differently to currently available therapies, which is why having options that address the hallmark characteristics of RRMS is so important,” said Giancarlo Comi, M.D., Honorary Professor of Neurology, Director of the Institute of Experimental Neurology at the Vita-Salute San Raffaele University in Milan. “Given its demonstrated efficacy and safety profile, Zeposia represents an important new treatment option that I am excited to offer my patients.”

Zeposia is the only approved S1P receptor modulator that offers RRMS patients with active disease an initiation with no first-dose observation required for the majority of patients.1 First-dose monitoring is only recommended for high-risk patients with certain pre-existing cardiac conditions. A dose escalation regimen from day 1 to day 7 should be used to reach the maintenance dose of Zeposia, as a transient decrease in heart rate and atrioventricular conduction delays may occur.

Zeposia demonstrated manageable safety and tolerability in the Phase 3 SUNBEAM and RADIANCE Part B trials. Zeposia is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, as listed in the Summary of Product Characteristics (SmPC); immunodeficient state; patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization or New York Heart Association (NYHA) Class III/IV heart failure; patients with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker; severe active infections, active chronic infections such as hepatitis and tuberculosis; active malignancies; severe hepatic impairment (Child-Pugh class C); and during pregnancy and in women of childbearing potential not using effective contraception. Zeposia is associated with the following Special Warnings and Precautions for Use: bradyarrhythmia, liver injury, immunosuppressive effects, increased risk of infections, progressive multifocal leukoencephalopathy, cutaneous neoplasms, macular oedema, posterior reversible encephalopathy syndrome, increased blood pressure, respiratory effects and severe increase in disability after stopping Zeposia. The most common adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain and hypertension.

“Multiple sclerosis is an unpredictable and often disabling disease that affects about 700,000 people in Europe. We are delighted by the news that there is now another treatment option available to potentially delay the progression of this debilitating disease,” said Pedro Carrascal, President of the European Multiple Sclerosis Platform.

About SUNBEAM™
​SUNBEAM is 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 HCI, 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 ARR 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 pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B Phase 3 trials.

About RADIANCE™
​RADIANCE Part B is 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 HCI, respectively) against weekly intramuscular AVONEX® (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people living with RMS 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, number of gadolinium-enhanced brain MRI lesions at month 24 and percent change from baseline in whole brain volume at month 24. 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 pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B Phase 3 trials.

About Multiple Sclerosis
​Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate — a process that's currently irreversible. MS affects 700,000 people in Europe and approximately 2.5 million people worldwide.

Relapsing remitting MS (RRMS) is characterized by clearly defined attacks of worsening neurologic function. These attacks — often called relapses, flare-ups or exacerbations — are followed by partial or complete recovery periods (remissions), during which symptoms improve partially or completely with no apparent progression of disease. At different points in time, RRMS can be characterized as active (with relapses and/or evidence of new MRI activity) or not active, as well as worsening (a confirmed increase in disability over a specified period of time following a relapse) or not worsening. RRMS is the most common disease course at the time of diagnosis. Approximately 85 percent of patients are initially diagnosed with RRMS, compared with 10-15 percent with progressive forms of the disease.

About Zeposia (ozanimod)
​Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system.

The U.S. Food and Drug Administration (FDA) approved Zeposia for the treatment of adults with relapsing forms of multiple sclerosis (RMS) in March 2020. ​ Zeposia is also in development for additional immune-inflammatory indications, including ulcerative colitis and Crohn's disease.

U.S. FDA-APPROVED INDICATION FOR ZEPOSIA

ZEPOSIA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Cautionary Statement Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that the outcome of pricing and reimbursement negotiations in individual countries in Europe may delay or limit the commercial potential of Zeposia (ozanimod) for the indication described in this release, and whether Zeposia (ozanimod) for the 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, 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.

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