Interferon beta-1a(Rentschler)

Retrospective analyses from the Phase 3 DAYBREAK open-label extension study showed more than 90% of participants who received Zeposia mounted a serologic response to COVID-19 vaccination All adverse events related to COVID-19 in vaccinated study participants were nonserious Data are among 13 abstracts being presented at ECTRIMS 2022 that further reinforce the safety and efficacy pro Zeposia and Bristol Myers Squibb’s commitment to the multiple sclerosis community PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced new retrospective analyses on serologic responses and clinical outcomes with COVID-19 vaccination in participants treated with Zeposia (ozanimod) from the ongoing Phase 3 DAYBREAK open-label extension (OLE) study in relapsing multiple sclerosis (MS). More than 92% (137/148) of all study participants in these analyses mounted a serological response following vaccination. In addition, among participants with prior COVID-19 exposure, seroconversion was observed in 100% (39/39) of individuals following full COVID-19 mRNA or non-mRNA vaccination. COVID-19-related adverse events were reported in 10% (15/148) of vaccinated participants (12/148 confirmed; 3/148 suspected), all of which were nonserious. The new analyses (Presentation #P1199) will be featured in the late-breaking research session on October 27, 2022, at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place in Amsterdam, the Netherlands. “These data are of clinical importance for physicians treating multiple sclerosis, because they provide a greater understanding of how COVID-19 infections and vaccinations interplay with Zeposia treatment,” said Bruce Cree, MD, PhD, MAS, study investigator and professor of Clinical Neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and Clinical Research Director, UCSF MS Center. “Regardless of prior COVID-19 exposure, most participants mounted an immune response following COVID-19 vaccination without experiencing adverse events, in contrast to some reports of other S1P modulators that described no response, adding insight to the treatment decision making process.” Additional key Bristol Myers Squibb data presentations at ECTRIMS 2022 include: Interim analyses of the ongoing Phase 3 DAYBREAK OLE study showed that 68% of participants were relapse-free and demonstrated an adjusted annualized relapse rate (ARR) of 0.099 at up to 74 months of treatment. Findings also showed long-term efficacy was sustained on MRI measures after 60 months of treatment, with a mean number of new and enlarging T2 lesions per scan of 0.98, and on disability progression in up to 74 months of treatment, with a 6-month confirmed disability progression of 14%. Treatment emergent adverse events (TEAEs) were reported in 88% of participants, with 14% of participants reporting serious TEAEs; 3.6% of participants discontinued treatment due to TEAEs. (Presentation #P334; Author: Krzysztof Selmaj) Post hoc analyses of the Phase 3 SUNBEAM, RADIANCE and DAYBREAK OLE studies demonstrated that a greater proportion of patients treated with Zeposia versus interferon beta-1a had a lower annualized rate of brain volume loss (SUNBEAM study, Month 12: 50.9% versus 37.5%, respectively; RADIANCE study, Month 24: 63.1% versus 50%, respectively). In patients continuously treated with Zeposia, those with low annualized rate of brain volume loss (ARBVL) showed higher cognitive processing speed as measured by the mean symbol digits modalities test compared with those with high ARBVL (SUNBEAM study into OLE study, Month 60: 52.7 versus 45.4; RADIANCE study into OLE study, Month 72: 50.5 versus 40.5, respectively). (Author: Bruno Brochet; e-Poster #EP1082) “We remain dedicated to pursuing pathbreaking science and collaborating with the scientific and patient communities to deepen our understanding on the use of our medicines and to help individuals with multiple sclerosis live healthier, more fulfilling lives,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “Our COVID-19 and disability progression findings, as well as our presentations demonstrating an association between Zeposia use and reduced brain volume loss along with improved cognitive processing speed, reinforce the importance of early intervention in the treatment of multiple sclerosis and Zeposia’s pro the treatment armamentarium.” Bristol Myers Squibb-sponsored abstracts featured at the ECTRIMS 2022 Congress: Serologic response and clinical outcomes of SARS-CoV-2 infection and vaccination in ozanimod-treated participants with relapsing multiple sclerosis Author: Bruce Cree Presentation number: P1199 Session: Poster Session 2 COVID-19 infections and vaccinations among patients receiving ozanimod in the DAYBREAK open-label extension trial Author: Bruce Cree Presentation number: P387 Session: Poster Session 1 Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Interim analysis of the DAYBREAK open-label extension study Author: Krzysztof Selmaj Presentation number: P334 Session: Poster Session 1 Correlations between early MRI parameters and long-term clinical outcomes in Phase 3 and open-label extension studies of ozanimod in relapsing multiple sclerosis Author: Douglas Arnold Presentation number: P358 Session: Poster Session 1 Proportion of relapsing MS patients with low vs high annualised whole brain volume atrophy rates after 5‒6 years of ozanimod and relationship to cognitive processing speed Author: Bruno Brochet e-Poster number: EP1082 Session: e-Poster Session Impact of ozanimod on absolute lymphocyte count and recovery in patients with relapsing multiple sclerosis Author: Krzysztof Selmaj e-Poster number: EP1071 Session: e-Poster Session Relationship between infections and absolute lymphocyte count during Phase 3 and open-label extension trials of ozanimod in patients with relapsing multiple sclerosis Author: Hans-Peter Hartung Presentation number: P707 Session: Poster Session 2 Safety patterns with ozanimod during Phase 3 and open-label extension trials in patients with relapsing multiple sclerosis Author: Krzysztof Selmaj Presentation number: P732 Session: Poster Session 2 NfL as a predictor of GdE lesions in patients with relapsing multiple sclerosis treated with ozanimod in the Phase 2 RADIANCE trial Author: Krzysztof Selmaj e-Poster number: EP1020 Session: e-Poster Session Post hoc analysis of cognitive processing speed at time of first confirmed relapse in patients with relapsing multiple sclerosis treated with ozanimod vs interferon β-1A in the Phase 3 SUNBEAM trial ​Author: John DeLuca e-Poster number: EP1116 Session: e-Poster Session Effect of disease modifying therapy on T2-flair-based neurodegenerative MRI outcomes: A longitudinal, real-world, US-based, multi-center multiple sclerosis study Author: Bruce Cree e-Poster number: EP1121 Session: e-Poster Session The impact of cognitive impairment on disease burden in Chinese patients with multiple sclerosis: A model simulation study Author: Qian Jiang e-Poster number: EP0870 Session: e-Poster Session Uncovering challenges in achieving health equity in multiple sclerosis care: A deep-dive into the experiences and perspectives of patients and their care teams in general neurology and MS specialty clinics Author: Mitzi Williams Presentation number: P110 Session: Poster Session 1 Bristol Myers Squibb thanks the patients and investigators who are participating in our Zeposia clinical trials. About DAYBREAK DAYBREAK is a Phase 3, multi-center, long-term open-label extension (OLE), randomized, double-blind, double-dummy, active-controlled, parallel group study to evaluate the safety and efficacy of Zeposia (ozanimod) administered orally to patients with relapsing forms of multiple sclerosis (MS). Eligible patients from the RADIANCE, SUNBEAM and RPC01-1001 trials diagnosed with relapsing forms of MS are enrolled to receive treatment until the end of the DAYBREAK trial or until the development program is discontinued. Patients in the trial are receiving Zeposia 0.92 mg (equivalent to ozanimod HCl 1 mg). About RADIANCE RADIANCE Part B was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral Zeposia (0.92 mg, equivalent to 1 mg) against weekly intramuscular AVONEX® (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people living with relapsing forms of MS across 150 sites in 21 countries. The primary endpoint of the trial was ARR over 24 months. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months. About SUNBEAM SUNBEAM was a pivotal, Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral Zeposia (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCl, respectively) against weekly intramuscular AVONEX® (interferon beta-1a) for at least a 12-month treatment period. The study included 1,346 people living with relapsing forms of MS across 152 sites in 20 countries. The primary endpoint of the trial was annualized relapse rates during the treatment period. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months, number of gadolinium-enhanced brain MRI lesions at Month 12 and percent change from baseline in whole brain volume at Month 12. Cortical grey and thalamic volume changes were also prospectively assessed versus active comparator. About Multiple Sclerosis Multiple sclerosis (MS) is a disabling, unpredictable disease in which the immune system attacks the protective myelin sheath that covers the nerves. The myelin damage disrupts communication between the brain and the rest of the body. Ultimately, the nerves themselves may deteriorate—a process that's currently irreversible. MS affects 700,000 people in Europe and approximately 2.5 million people worldwide. Relapsing forms of MS, including clinically isolated syndrome, relapsing remitting disease and active secondary progressive disease, is characterized by clearly defined attacks of worsening neurologic function. These attacks—often called relapses, flare-ups or exacerbations—are followed by partial or complete recovery periods. During these recovery periods, also called remissions, symptoms improve partially or completely with no apparent progression of disease. Since MS relapses are unpredictable, patients can feel frustrated, stressed, or scared when they occur. Relapsing forms of MS are the most common disease course at the time of diagnosis. Approximately 85% of patients are initially diagnosed with relapsing forms of MS, compared with 10-15% with progressive forms of the disease. About Zeposia (ozanimod) Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Zeposia blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which Zeposia exerts therapeutic effects in multiple sclerosis (MS) is unknown but may involve the reduction of lymphocyte migration into the central nervous system. The U.S. Food and Drug Administration approved Zeposia for the treatment of adults with relapsing forms of multiple sclerosis in March 2020 and adults with moderately to severely active UC in May 2021. The European Commission approved Zeposia for the treatment of adult patients with relapsing remitting multiple sclerosis with active disease as defined by clinical or imaging features in May 2020 and for the treatment of adults with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent in November 2021. U.S. FDA APPROVED INDICATIONS ZEPOSIA® (ozanimod) is indicated for the treatment of: Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Moderately to severely active ulcerative colitis (UC) in adults. IMPORTANT SAFETY INFORMATION Contraindications: Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker Patients with severe untreated sleep apnea Patients taking a monoamine oxidase (MAO) inhibitor Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA. Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA. Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated. In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects. Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA. Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability. PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation. If confirmed, treatment with ZEPOSIA should be discontinued. Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals: with significant QT prolongation with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block Liver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant liver disease. Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting . Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and managed appropriately. Certain foods that may contain very high amounts of tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods containing a very large amount of tyramine while taking ZEPOSIA. Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated. Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued. Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued. Unintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended. Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation. Immune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA. Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache. Use in Specific Populations: Hepatic Impairment: Use is not recommended. For additional safety information, please see the full Prescribing Information and Medication Guide. Bristol Myers Squibb: Pioneering Paths Forward in Immunology to Transform Patients’ Lives Bristol Myers Squibb is inspired by a single vision – transforming patients’ lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can take a toll on their physical, emotional and social well-being, making simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, and our passion to help patients, the company continues to pursue pathbreaking science with the goal of delivering meaningful solutions that address unmet needs in rheumatology, gastroenterology, dermatology and neurology. We follow the science, aiming to tailor therapies to individual needs, improve outcomes and expand treatment options by working to identify mechanisms with the potential to achieve long-term remission – and perhaps even cures – in the future. By building partnerships with researchers, patients and caregivers to deliver innovative treatments, Bristol Myers Squibb strives to elevate patient care to new standards and deliver what matters most – the promise of living a better life. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that any marketing approvals, if granted, may have significant limitations on their use, and that such product candidate for the indication described in this release, may not be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2021, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news View source version on businesswire.com: Contacts Bristol Myers Squibb Media Inquiries: media@bms.com Investors: investor.relations@bms.com Source: Bristol Myers Squibb View this news release online at:

Company’s scientific leadership will be highlighted in 39 abstracts presented across its multiple sclerosis (MS) portfolio Data on investigational BTK inhibitor evobrutinib demonstrate long-term disease stability in people living with relapsing MS (RMS) Phase IV study highlights improvement in measures of Quality of Life in people living with RMS after two years of treatment with MAVENCLAD® (cladribine) tablets ROCKLAND, Mass--(BUSINESS WIRE)-- EMD Serono, the Healthcare business sector of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced the company will present 39 abstracts at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held October 26-28, 2022 in Amsterdam, the Netherlands. The breadth of data highlights the Company’s scientific leadership in multiple sclerosis (MS) and includes a presentation on a clinical trial with long-term data on Expanded Disability Status Scale (EDSS) scores in people with relapsing MS (RMS) treated with evobrutinib, an investigational agent, as well as new data demonstrating MAVENCLAD® (cladribine) tablets improved Quality of Life (QoL) in people with highly active RMS over two years. Additionally, a two-year follow-up study showed the onset of action on the reduction of MRI lesions with MAVENCLAD being maintained from Month 2 through two years. “Multiple sclerosis has a profound impact on quality of life and improving this through therapy is often the most important outcome for people living with MS,” said Gavin Giovannoni, Professor of Neurology, Queen Mary University of London. “The data presented at ECTRIMS further substantiate the therapeutic benefit of MAVENCLAD by improving Quality of Life measures over two years, combined with new evidence that the early effect on MRI lesions is maintained over that period.” In the final analysis of the open-label, single-arm, multicenter, Phase IV CLARIFY-MS study, statistically significant (p≤0.0001) improvements from baseline were observed for Multiple Sclerosis Quality of Life-54 (MSQoL-54) physical and mental health composite scores (mean changes of 4.86 and 4.80, respectively; p<0.0001). Changes in MSQoL-54 composite scores were consistent across treatment naïve and prior disease-modifying treatment (DMT) subgroups. Annualized relapse rate was 0.13 in all patients (0.08 in patients who had not received DMT prior to receiving MAVENCLAD) and median EDSS was unchanged over two years. No new safety concerns emerged. Also to be presented are new MRI outcomes data from the Phase IV MAGNIFY-MS study, which demonstrated an onset of action from Month 2 with sustained reduction in MRI lesion counts maintained out to two years in people with highly active RMS treated with MAVENCLAD. The proportion of lesion-free patients increased from 47% at baseline to 86.2% at the end of the study (Month 18–24). In the study, MRI lesions at baseline were compared over multiple time periods, from initial screening to Month 24. Over the two years, the benefit:risk pro MAVENCLAD remained unchanged and in line with observations made during the clinical trial program. Additionally, updated post-approval safety data will be presented based on an analysis of 56,300 patients who received MAVENCLAD post-approval, representing 95,664 patient-years of experience, as of July 2022. The study found the safety pro MAVENCLAD is consistent with findings from the clinical development program and the CLARIFY-MS and MAGNIFY-MS studies. “The breadth of our data at ECTRIMS exemplifies our commitment to pushing forward scientific innovation with the development of evobrutinib, while generating new, meaningful data to demonstrate the safety pro effectiveness of MAVENCLAD,” said Jan Klatt, Senior Vice President, Head of Development Unit Neurology & Immunology, Merck KGaA, Darmstadt, Germany. “Our goal is to ensure people living with MS, and those who treat them, have the information they need to manage their MS today and in the future.” Beyond the MAVENCLAD and evobrutinib data presented, EMD Serono will have several Company events, along with additional data from its MS portfolio at ECTRIMS 2022. Company activities at ECTRIMS 2022: “Connecting the dots: immune cells and CNS inflammation” co-chaired by Professor Gavin Giovannoni, MBBCh, PhD, FCP (Neurol., SA), FRCP, FRCPath, Blizard Institute, Barts and the London School of Medicine and Dentistry, UK, and Celia Oreja-Guevara, MD, PhD, Hospital Clínico San Carlos, Madrid, Spain (October 26, 2022, 13:15-14:15 CEST) “New tools for new challenges in multiple sclerosis” chaired by Stephen Krieger, MD, Mount Sinai Hospital, New York, NY, USA (October 28, 2022, 14:15-15:15 CEST) Product Theater: Early Experience with MAVENCLAD by Ravi Dukkipati, MD, WellSpan Neurology, York, PA, USA Below is the full list of Company-related abstracts accepted for presentation at ECTRIMS 2022: Abstract Name Authors ID Presentation Details MAVENCLAD Poster Presentations Improvements in Quality of Life Over 2 Years in Patients Treated With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: Final Analysis of CLARIFY-MS Solari A, Montalban X, Lechner-Scott J, Piehl F, Brochet B, Langdon D, Hupperts R, Selmaj K, Havrdova EK, Patti F, Brieva L, Maida EM, Alexandri N, Smyk A, Nolting A, Keller B, on behalf of the CLARIFY Investigators P108 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Jeannette Lechner-Scott Early Onset of Action and Sustained Efficacy of MRI Outcomes during Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-year MAGNIFY-MS Study De Stefano N, Achiron A, Barkhof F, Chan A, Derfuss T, Hodgkinson S, Leocani L, Montalban X, Prat A, Schmierer K, Sellebjerg F, Vermersch P, Wiendl H, Keller B, Smyk A, Gardner L P717 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Nicola De Stefano Updated Post-Approval Safety of Cladribine Tablets in the Treatment of Multiple Sclerosis, With Particular Reference to Liver Safety Giovannoni G, Leist T, Jack D, Galazka A, Nolting A P341 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Gavin Giovannoni High Adherence and Minimal Delays of Year 2 Treatment in People with Multiple Sclerosis Treated with Cladribine Tablets: Results from Multi-Country Patient Support Programmes Oh J, Ayer M, Alroughani R, Lemieux C, Morgan K, D’Eramo M, Vella T, Boshra A, de Souza S, Verdun di Cantogno E, Sabidó M P727 Session: 2 Date: October 27, 2022 Time: 17:00 CEST Presenter: Jiwon Oh Treatment Emergent Adverse Events Experienced Early and Transiently in the Treatment Course with Cladribine Tablets: Data from the CLEVER Real-World Study Ziemssen T, Posevitz-Fejfar, Wagner T, Übler S, Richter J, Müller B, Penner I-K P772 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Talf Ziemssen Maven4: Phase IV Non-Interventional, Prospective, Spanish Multicenter Study to Evaluate Cladribine Tablets Long Term Effectiveness on Real-World Clinical Practice Saiz A, Aladro Benito Y, Costa-Frossard F, Sánchez Magro I, Rodríguez Antigüedad A P774 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Albert Saiz Cladribine Protects SH-SY5Y Neuron-Like Cells from Oxidative Stress Conditions In Vitro Eixarch H, Calvo-Barreiro L, Fissolo N, Boschert U, Comabella M, Montalban X, Espejo C P784 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Herena Eixarch Real-World Use of Cladribine Tablets (Completion Rates and Treatment Persistence) in Patients With Multiple Sclerosis in England: The CLARENCE Study Brownlee W, Amin A, Herbert A, Ashton L P762 Session: 2 Date: October 27, 2022 Time: 17:00 CEST Presenter: Wallace Brownlee Decision-making Factors in Patient Choice to Initiate Treatment with Cladribine: A Preliminary Baseline Analysis From the STATURE Study Allan M, Grech L, Cartwright A, Harding J, Mardan J, O’Maley J, Savickas S, Sharma M, Murambiwa P, Stockle P, Bardsley B, Butler E P304 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Michelle Allan Assessment of Treatment Satisfaction Across Oral DMTs for Multiple Sclerosis: a Preliminary Baseline Analysis from the STATURE Study. Grech L, Allan M, Cartwright A, Harding J, Mardan J, O’Maley T, Savickas S, Sharma M, Murambiwa P, Stockle P, Bardsley B, Butler E EP1086 Session: ePoster Date: October 26-28, 2022 A Real-World Study of Four-Year Follow Up Study of Patients Treated with Oral Cladribine From 2018-2022 O’Neill DTD, Sharma M, Dong G, Hodgkinson SJ EP1132 Session: ePoster Date: October 26-28, 2022 A Study of Activated and Naïve T Regs and B Cell Subsets For 30 Months After the Use of Cladribine Hodgkinson SJ, O’Neill DTD, Sharma M, Dong G, Verma ND, Al-atiyah R, Hall BM P704 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Suzanna Hodgkinson CLADCOMS - CLADribine Tablets Long-Term Control of MS – a Post-Marketing Investigator Driven Study Fink K, Nilsson P, Alonso L, Sveningsson A, Gunnarsson M, Lange N, Ayad A, Vrethem M, Burman J, Lycke J, Piehl F EP1060 Session: ePoster Date: October 26-28, 2022 Clinical Effectiveness and Safety of Cladribine Tablets for Patients Treated at least 12 Months in the Swedish Post-Market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Rosengren V, Ekström E, Forsberg L, Hillert J, Nilsson P, Dahle C, Svenningsson A, Lycke J, Landtblom A-M, Burman J, Martin C, Sundström, Gunnarsson M, Piehl F, Olsson T P728 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Linda Forsberg SARS-CoV2 Exposure Rates and Serological Response of People Living With MS Longinetti E, Asplund K, Kockum I, Englund S, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, Hillert J, Langer-Gould A, Lycke J, Nilsson P, Salzer J, Svenningsson A, Mellergård J, Frisell T, Olsson T, Piehl F P558 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Elisa Longinetti COVID-19 Humoral and T-cell Mediated Vaccination Responses in People with Multiple Sclerosis Vickaryous N, Rios F, Schalk L, Asardag AN, George K, Kang A, Baker D, Giovannoni G, Dobson R P781 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Nikki Vickaryous Differences Between Clinical Trials and “Real-World” Use of Disease Modifying Therapies: Insights from the UK OPTIMISE:MS Pharmacovigilance Study Dobson R, Matthews P, Miller A, Pindoria J, Waddingham E P763 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Ruth Dobson Cladribine Treatment Exerts Specific Effects on Memory B Cell Immunoglobulin Repertoires in Multiple Sclerosis Patients Ruschil C, Gabernet G, Kemmerer CL, Ziemann U, Nahnsen S, Kowarik MC EP1115 Session: ePoster Date: October 26-28, 2022 Presenter: Christoph Ruschil Cladribine Effects on T and B Cell Subsets and T Cell Reactivity in Multiple Sclerosis Hansen RH, von Essen MR, Mahler MR, Cobanovic S, Binko TS, Sellebjerg F P697 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Rikke Holm Hansen Safety and Efficacy of Cladribine Therapy Following a Treatment with Anti-CD20 Compounds in Relapsing Multiple Sclerosis Patients: A Pilot Study Sacco R, Disanto G, Pravatà E, Gobbi C, Zecca C EP1068 Session: ePoster Date: October 26-28, 2022 Evobrutinib Poster Presentations Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, Maintains Lowered Serum Neurofilament Light Chain Levels Over 2.5 Years of Treatment, in Patients With Relapsing Multiple Sclerosis Kuhle J, Kappos L, Montalban X, Benkert P, Li Y, Thangavelu K, Hyvert Y, Tomic D EP1021 Session: ePoster Date: October 26-28, 2022 Presenter: Jens Kuhle MRI and Clinical Outcomes of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis Over 2.5 Years of the Open-label Extension to a Phase II Trial Vermersch P, Arnold D, Wolinsky JS, Havrdova E, Kinkolykh A, Hyvert Y, Tomic D, Montalban X P731 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Patrick Vermersch Evobrutinib Exert a Therapeutic Action on EAE by Increasing the Peripheral and Central Classical Dendritic Cell Number and Maturation Serrano-Regal MP, Calahorra L, Alonso-García I, Grenningloh R, Boschert U, Haselmayer P, Ortega MC, Machín-Díaz I, Camacho-Toledano C, García-Arocha J, Clemente D P307 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Mari Paz Serrano-Regal Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, Acts on Microglia: Implications in the Treatment of Progressive Mechanisms in Multiple Sclerosis Geladaris A, Torke S, Grenningloh R, Boschert U, Brück W, Weber MS P693 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Anastasia Geladaris B cells infiltrating the MS brain: from local maturation to targeting by evobrutinib Bogers L, van Langelaar J, Rijvers L, Engelenburg HJ, Melief M-J, Wierenga-Wolf AF, Rip J, Blok KM, de Vries HE, Hendriks RW, Boschert U, Smolders J, van Luijn MM P147 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Laurens Bogers Immune response following mRNA COVID-19 vaccination in patients with multiple sclerosis treated with the Bruton’s tyrosine kinase inhibitor evobrutinib Bar-Or A, Cross AH, Cunningham A, Hyvert Y, Seitzinger A, Drouin EE, Alexandri N, Tomic D, Montalban X P1188 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Amit Bar-Or Rebif® (interferon beta-1a) Subcutaneous Injection Poster Presentations Exploring the Relationship Between Serum GDF-15 and Disease Stability in Patients with a First Clinical Demyelinating Event Treated with Subcutaneous Interferon β-1a or Placebo in the REFLEX Study Coray M, Freedman MS, Barkhof F, Comi G, De Stefano N, Kappos L, Enz L, Seitzinger A, Jack D, Kuhle J, Mehling M EP1027 Session: ePoster Date: October 26-28, 2022 Presenter: Mali Coray Evolution of the RebiSmart® Autoinjector Device in Support of Adherence to Subcutaneous Interferon Beta-1a Therapy for Relapsing Multiple Sclerosis Arnaud L, Keiser M, Henninger E, Piras F, Seitzinger A, Jack D, Le Masne Q EP1079 Session: ePoster Date: October 26-28, 2022 Presenter: Dominic Jack Validation of a Semi-Automated Method to Quantify Lesion Volume Changes in Multiple Sclerosis on 2D Proton Density- Weighted Images Using Subtraction Imaging Mattiesing RM, Stel S, Mangroe AS, Brouwer I, Versteeg A, van Schijndel RA, Uitdehaag BMJ, Barkhof F, Vrenken H P634 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Rozemarijn M Mattiesing Expression of peripheral blood IFN-inducible genes predicts treatment outcome in patients with secondary progressive multiple sclerosis treated with IFN-beta-1a Gurevich M, Zilkha-Falb R, Menascu S, Magalashvili D, Dolev M, Sonis P, Mandel M, Achiron A P353 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Michael Gurevich Non-Product Specific Poster Presentations DISCOntinuation of disease-modifying therapies in MS (DISCOMS) Extension – Study Design and Baseline Demographics to Date Engebretson E, Cutter G, Fox R, Kister I, Miller A, Morgan C, Seale R, Corboy JR EP1089 Session: ePoster Date: October 26-28, 2022 Expert Opinion on the Use of Contraception in People with Multiple Sclerosis Hillert J, Bove R, Haddad L, Hellwig K, Houtchens M, Magyari M, Mercki G, Montgomery S, Nappi R, Stenager E, Thompson H, Tulek Z, Verdun di Cantogno E, Simoni M P080 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Jan Hillert Single-Cell RNA Sequencing of Peripheral CD8+ T Cells of MS-Discordant Monozygotic Twins Reveals Disease-Associated Alterations In Immune Signaling Kavaka V, Mutschler L, Eglseer K, Flierl-Hecht A, Kümpfel T, Hohlfeld R, Kerschensteiner M, Gerdes L.A, Beltran E P159 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Vladyslav Kavaka Caregiver Burden and Associated Factors Among Caregivers of Persons with Multiple Sclerosis: Application of a Specific Instrument Vanotti S, Roman MS, Ferrandina F, Bauer J, Rosa R, Casas Parera I, Saladino ML, Caceres F EP0864 Session: ePoster Date: October 26-28, 2022 Presenter: Sandra Vannoti Evolutionarily Conserved Signatures of Microglia in Health and Disease Salinas V, Manouchehri N, Hussain R, Stuve O P131 Session: 1 Date: October 26, 2022 Time: 16:30- 18:30 CEST Presenter: Victor Salinas Peripheral Blood Immune Markers Associated With Immunosenescence in Multiple Sclerosis and Healthy Controls Carpentier Solorio Y, Daigneault A, Tastet O, Clénet M-L, Farzam-kia N, Levert A, Da Cal S, Clément W, Jamann H, Laurent C, Mamane VH, Ouedraogo O, Moratalla AC, Balthazard R, Lahav B, Prat A, Girard J-M, Duquette P, Rousseau M-C, Arbour N, Larochelle C P545 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Catherine Larochelle Chemerin Correlates with MS Progression Parameters and Affects Intracellular Metabolism in Human Microglia and Macrophages Loonstra FC, van der Pol SM, Falize KF, van Heertum T, de Ruiter LR, Schoonheim MM, Killestein J, Uitdehaag BMJ, Kooij G, de Vries HE, Rijnsburger M P551 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Presenter: Merel Rijnsburger Amyloid and some tau Proteinopathy are Observed in a Subset of Individuals with Multiple Sclerosis Taga M, Duquesne L, Lee A, Sigalov A, Peralta Cruz F, De Jager P P1204 Session: 2 Date: October 27, 2022 Time: 17:00- 19:00 CEST Non-Product Specific Oral Presentations Biological Roles of Myeloid Cell Subsets During CNS Inflammation Manouchehri N, Victor, Hussain RZ, Stuve O O124 Session: Young Scientific Investigators' Session 3: Long-term outcomes and safety Date: October 27, 2022 Time: 15:00- 16:00 CEST Presenter: Navid Manouchehri About Evobrutinib Evobrutinib is an oral, highly selective CNS-penetrant inhibitor of Bruton’s tyrosine kinase (BTK) in clinical development as a potential treatment for relapsing multiple sclerosis (RMS). It is the first BTK inhibitor to demonstrate clinical efficacy in the largest Phase II study with follow-up beyond three years as well as demonstrate an impact on early biomarkers of ongoing central inflammation that correlate with disease progression. Evobrutinib is designed to modulate B cell responses such as proliferation and antibody and cytokine release, as well as modulate macrophage/microglia activation. It significantly reduced SEL volume and levels of blood NfL, markers of ongoing central inflammation and neurodegeneration that predict long-term disability. Evobrutinib was optimized for efficacy through the most comprehensive BTK inhibitor dose-finding study in RMS which demonstrated 75mg twice-daily dosing achieves maximal efficacy across endpoints by sustaining BTK inhibition throughout the dosing interval (>95% BTK occupancy maintained in 98% of patients before next dose). It is currently under clinical investigation and is not approved for any use anywhere in the world. About MAVENCLAD® MAVENCLAD, approved by the U.S. Food and Drug Administration (FDA) on March 29, 2019, is the first and only short-course oral therapy for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS). Patients should follow healthcare provider instructions including cancer screening, contraception and blood tests. The approved dose of MAVENCLAD is 3.5 mg per kg body weight over two years, administered as one treatment course of 1.75 mg per kg per year, each consisting of two treatment weeks. The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes. MAVENCLAD causes a dose-dependent reduction in lymphocyte counts followed by recovery. Because cladribine is cytotoxic, special handling and disposal instructions should be followed. MAVENCLAD has been approved in over 80 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit for more information. IMPORTANT SAFETY INFORMATION WARNING: MALIGNANCIES and RISK OF TERATOGENICITY Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with MAVENCLAD in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. Stop MAVENCLAD if the patient becomes pregnant CONTRAINDICATIONS Patients with current malignancy. Pregnant women, and women and men of reproductive potential who do not plan to use effective contraception during and for 6 months after the last dose in each treatment course. May cause fetal harm. Patients with human immunodeficiency virus (HIV). Patients with active chronic infections (e.g., hepatitis or tuberculosis). Patients with a history of hypersensitivity to cladribine. Women intending to breastfeed while taking MAVENCLAD tablets and for 10 days after the last dose. WARNINGS AND PRECAUTIONS Malignancies: Treatment with MAVENCLAD may increase the risk of malignancy. After the completion of 2 treatment courses, do not administer additional MAVENCLAD treatment during the next 2 years. In clinical studies, patients who received additional MAVENCLAD treatment within 2 years after the first 2 treatment courses had an increased incidence of malignancy. The risk of malignancy with reinitiating MAVENCLAD more than 2 years after the completion of 2 treatment courses has not been studied. Follow standard cancer screening guidelines in patients treated with MAVENCLAD. Risk of Teratogenicity: MAVENCLAD may cause fetal harm when administered to pregnant women. In females of reproductive potential, exclude pregnancy before initiation of each treatment course of MAVENCLAD and prevent by the use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose of each treatment course. Women who become pregnant during treatment with MAVENCLAD should discontinue treatment. Lymphopenia: MAVENCLAD causes a dose-dependent reduction in lymphocyte count. In clinical studies, 87% of MAVENCLAD-treated patients experienced lymphopenia. The lowest absolute lymphocyte counts occurred approximately 2 to 3 months after the start of each treatment course and were lower with each additional treatment course. Concomitant use of MAVENCLAD with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects. Monitor lymphocyte counts before and during treatment, periodically thereafter, and when clinically indicated. Infections: MAVENCLAD can reduce the body's immune defense and may increase the likelihood of infections. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% of patients treated with placebo in clinical studies. The most frequent serious infections included herpes zoster and pyelonephritis. Single fatal cases of tuberculosis and fulminant hepatitis B were reported in the clinical program. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting MAVENCLAD. Screen patients for latent infections; consider delaying treatment until infection is fully controlled. Vaccinate patients antibody-negative to varicella zoster virus prior to treatment. Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter. Monitor for infections. In patients treated with parenteral cladribine for oncologic indications, cases of progressive multifocal leukoencephalopathy (PML) have been reported. No case of PML has been reported in clinical studies of cladribine in patients with MS. Hematologic Toxicity: In addition to lymphopenia, decreases in other blood cells and hematological parameters have been reported with MAVENCLAD in clinical studies. In general, mild to moderate decreases in neutrophil counts, hemoglobin levels, and platelet counts were observed. Severe decreases in neutrophil counts were observed in 3.6% of MAVENCLAD-treated patients, compared to 2.8% of placebo patients. Obtain complete blood count (CBC) with differential including lymphocyte count before and during treatment, periodically thereafter, and when clinically indicated. Risk of Graft-versus-Host Disease With Blood Transfusions: Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of nonirradiated blood in patients treated with cladribine for non-MS treatment indications. Liver Injury: In clinical studies, 0.3% of MAVENCLAD-treated patients had liver injury (serious or causing treatment discontinuation) compared to 0 placebo patients. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment. Discontinue if clinically significant injury is suspected. Hypersensitivity: In clinical studies, 11% of MAVENCLAD-treated patients had hypersensitivity reactions, compared to 7% of placebo patients. Hypersensitivity reactions that were serious and/or led to discontinuation of MAVENCLAD, occurred in 0.5% of MAVENCLAD-treated patients, compared to 0.1% of placebo patients. If a hypersensitivity reaction is suspected, discontinue MAVENCLAD therapy. Do not use MAVENCLAD in patients with a history of hypersensitivity to cladribine. Cardiac Failure: In clinical studies, one MAVENCLAD-treated patient experienced life-threatening acute cardiac failure with myocarditis, which improved after approximately one week. Cases of cardiac failure have also been reported with parenteral cladribine used for treatment indications other than multiple sclerosis. Adverse Reactions: The most common adverse reactions with an incidence of >20% for MAVENCLAD are upper respiratory tract infection, headache, and lymphopenia. Drug Interactions/Concomitant Medication: Concomitant use of MAVENCLAD with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Acute short-term therapy with corticosteroids can be administered. Avoid concomitant use of certain antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD. Use in Specific Populations: Studies have not been performed in pediatric or elderly patients, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended. Please see the full Prescribing Information, including boxed WARNING for additional information. About Rebif® (interferon beta-1a) Rebif (interferon beta-1a) 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. It is used to decrease the frequency of relapses and delay the occurrence of some of the physical disability that is common in people with MS. IMPORTANT SAFETY INFORMATION: Rebif is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation. Rebif should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression, suicidal ideation, and suicide attempts have been reported to occur with increased frequency in patients receiving interferon compounds, including Rebif. Severe liver injury, including some cases of hepatic failure requiring liver transplantation, has been reported rarely in patients taking Rebif. The potential for liver injury should be considered when used in combination with other products associated with liver injury. Monitor liver function tests and patients for signs and symptoms of hepatic injury. Consider discontinuing Rebif if hepatic injury occurs. Anaphylaxis and other allergic reactions (some severe) have been reported as a rare complication of Rebif. Discontinue Rebif if anaphylaxis occurs. In controlled clinical trials, injection site reactions occurred more frequently in Rebif-treated patients than in placebo-treated and Avonex-treated patients. Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting. Do not administer Rebif into affected area until fully healed; if multiple lesions occur, discontinue Rebif until skin lesions are healed. Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in Rebif-treated patients. In controlled clinical trials, leukopenia occurred at a higher frequency in Rebif-treated patients than in placebo and Avonex-treated patients. Thrombocytopenia and anemia occurred more frequently in 44 mcg Rebif-treated patients than in placebo-treated patients. Patients should be monitored for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended. Cases of thrombotic microangiopathy (TMA), some fatal, have been reported with interferon beta products, including Rebif, up to several weeks or years after starting therapy. Discontinue Rebif if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated. Caution should be exercised when administering Rebif to patients with pre-existing seizure disorders. Seizures have been temporally associated with the use of beta interferons, including Rebif, in clinical trials and in postmarketing reports. The most common side effects with Rebif are injection-site disorders, headaches, influenza-like symptoms, abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities. Epidemiological data do not suggest a clear relationship between interferon beta use and major congenital malformations, but interferon beta may cause fetal harm based on animal studies. Data from a large human population-based cohort study, as well as other published studies over several decades, have not identified a drug-associated risk of major birth defects with interferon beta products during early pregnancy. Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta products in pregnancy have been inconsistent. Please see the full Prescribing Information for additional information: About Multiple Sclerosis Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common non-traumatic, disabling neurological disease in young adults. It is estimated that approximately 2.8 million people have MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common. EMD Serono, Inc. and Multiple Sclerosis For more than 20 years, EMD Serono has been relentlessly focused on understanding the journey people living with MS face in order to create a meaningful, positive experience for them and the broader MS community. However, there is still much that is unknown about this complex and unpredictable disease. EMD Serono is digging deeper to advance the science. About EMD Serono, Inc. EMD Serono - the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada - aspires to create, improve and prolong life for people living with difficult-to-treat conditions like infertility, multiple sclerosis and cancer. The business is imagining the future of healthcare by working to translate the discovery of molecules into potentially meaningful outcomes for people with serious unmet medical needs. EMD Serono’s global roots go back more than 350 years with Merck KGaA, Darmstadt, Germany. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations in Massachusetts. . About Merck KGaA, Darmstadt, Germany Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across life science, healthcare and electronics. Around 60,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck KGaA, Darmstadt, Germany, generated sales of € 19.7 billion in 66 countries. The company holds the global rights to the name and trademark “Merck” internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA, Darmstadt, Germany, operate as MilliporeSigma in life science, EMD Serono in healthcare and EMD Electronics in electronics. Since its founding in 1668, scientific exploration and responsible entrepreneurship have been key to the company’s technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company. View source version on businesswire.com: Contacts alice.mcgrail@emdserono.com Phone: 1-781-681-2886 Source: EMD Serono View this news release online at: