Interferon beta-1a(Rentschler)

Final safety and efficacy results from the Phase 3 EVOLVE-MS-1 trial demonstrate decreases in disease activity and favorable tolerability for VUMERITY®(diroximel fumarate) consistent with previous assessments Patient-reported outcomes favored TYSABRI® (natalizumab) compared to Ocrevus® (ocrelizumab); new insights on subcutaneous administration one year after approval in Germany Data on interferon exposure during pregnancy showed that treatment with PLEGRIDY® (peginterferon beta-1a) or AVONEX® (interferon beta-1a) did not negatively impact child development CAMBRIDGE, Mass., Oct. 26, 2022 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced new data from its industry-leading portfolio of multiple sclerosis (MS) therapies being presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting October 26-28, 2022. The presentations include the final safety and efficacy results of the VUMERITY® (diroximel fumarate) EVOLVE-MS-1 study, as well as a matching analysis comparing treatment with VUMERITY to Ponvory® (ponesimod) and Aubagio® (teriflunomide); patient-reported outcomes and an analysis of the proprietary StratifyJCV™ assay for TYSABRI® (natalizumab); a study evaluating treatment with TECFIDERA® (dimethyl fumarate) to prevent first clinical manifestation of MS for people with radiologically isolated syndrome; and studies assessing the impact of PLEGRIDY® (peginterferon beta-1a) and AVONEX® (interferon beta-1a) on pregnancy, breastfeeding and child development. “Presentations at this year’s ECTRIMS meeting highlight Biogen’s commitment to pursuing research that has a meaningful impact on patients,” said Maha Radhakrishnan, M.D., Chief Medical Officer at Biogen. “These new data provide patients and healthcare professionals with further insight on the safety and efficacy of Biogen’s robust MS portfolio to help inform treatment decisions throughout the lifelong MS journey, from the earliest phase of the disease to important milestones such as pregnancy.” Final Safety and Efficacy Results of VUMERITY EVOLVE-MS-1 Study Reported Presentations including data from EVOLVE-MS-1 and OPTIMUM clinical studies further support the safety and efficacy of VUMERITY: Final safety and efficacy results from EVOLVE-MS-1 demonstrate decreases in disease activity and favorable tolerability for VUMERITY in 1,057 patients over 96 weeks, in line with previous assessments. The reduction in annualized relapse rate (ARR) was 81.6%, the estimated proportion of patients who were relapse-free was 82.4%, and the estimated proportion with no evidence of disease activity (NEDA-3) was 41.1%. While 24.3% of patients discontinued treatment, discontinuation due to gastrointestinal adverse events (0.7%) and flushing (0.5%) were low. A matching-adjusted indirect comparison was done between VUMERITY (EVOLVE-MS-1) and Ponvory and Aubagio (OPTIMUM) clinical studies for ARR, 12-week confirmed disability progression (CDP), 24-week CDP, absence of gadolinium-enhancing (Gd+) T1 lesions and absence of new/enlarging T2 lesions. After weighting for cross-trial differences, VUMERITY was associated with a higher proportion of patients free of Gd+ T1 lesions and new/enlarging T2 lesions at the end of follow-up compared to Ponvory, with similar efficacy for ARR and 12- and 24-week CDP. VUMERITY had greater efficacy than Aubagio for all clinical and radiological outcome measures, except for 24-week CDP, in which there was similar efficacy. Studies Highlight Patient-Reported Outcomes for TYSABRI; Analysis Shows Impact of StratifyJCV Assay Two presentations highlight improvements in patient-reported outcomes following treatment with TYSABRI along with preference and satisfaction for the TYSABRI subcutaneous (SC) route of administration: The results of recent survey analysis, which included TYSABRI [n=52] and Ocrevus (ocrelizumab)-treated [n=92] relapsing-remitting multiple sclerosis (RRMS) patients aged 21 and older who had taken at least one prior disease modifying treatment (DMT), found more patients treated with TYSABRI versus Ocrevus reported improvements in disease activity (84.6% vs 59.8%), emotional symptoms (73.1% vs 35.9%), physical symptoms (69.2% vs 43.5%), cognitive symptoms (61.5% vs 32.6%) and social roles/activities (71.2% vs 35.9%). In addition, more patients treated with TYSABRI reported their DMT met or exceeded treatment expectations in comparison to those treated with Ocrevus (96.2% vs 72.8%). In the first interim analysis of 206 patients in the observational, prospective, multi-center SISTER study in Germany, the TYSABRI SC route of administration was preferred by individuals (89.6%; 163 patients) compared with intravenous administration; nearly all patients receiving SC treatment expressed satisfaction with their choice (98.7%; 156 patients) and the most frequent reasons for SC preference were shorter and more convenient administration. The TYSABRI SC administration is available in 26 countries and over 16,000 patients have been treated with SC therapy.1 “Given the recent introduction of natalizumab subcutaneous administration in Europe, these findings validate clinical study data with real-world insights,” said Prof. Ralf Gold, Ruhr-University Bochum, Bochum, Germany. “In our study, we found that nearly 90% of patients prefer subcutaneous administration given its shorter duration and convenience of dosing.” Separately, an analysis assessed utilization of Biogen’s StratifyJCV™ -- a proprietary antibody assay used to detect the presence of anti-JC virus (JCV) antibodies in serum and to quantify antibody index values, which are correlated to progressive multifocal leukoencephalopathy (PML) risk in patients treated with TYSABRI. More than 2 million StratifyJCV tests have been conducted worldwide. Aggregated data of the results of 845,498 StratifyJCV tests conducted from January 2015 to December 2021 showed a decrease in percentage of JCV-positive index results >1.5 in retests, from 15% in 2015 to 8% in 2021, demonstrating that healthcare professionals are using the assay to appropriately identify, monitor and manage patients on TYSABRI. Effect of TECFIDERA on Radiologically Isolated Syndrome Reported for the First Time Results of the Assessment of TECFIDERA in Radiologically Isolated Syndrome (ARISE) study, a placebo-controlled, multi-center, double-blinded clinical trial, will be presented in the late-breaking section. ARISE investigated the impact of therapeutic intervention in preventing the first clinical manifestation of MS for people with radiologically isolated syndrome (RIS). ARISE enrolled 87 patients who were randomized to TECFIDERA or placebo and treated for up to 96 weeks. Researchers found treatment with TECFIDERA resulted in an 82% risk reduction relative to placebo in the prevention of a first clinical event related to CNS demyelination. Impact of PLEGRIDYand AVONEXon Pregnancy, Breastfeeding and Child Development Two presentations assessed the impact of interferon exposure on pregnancy, breastfeeding and child development. Data from the PRIMA post-authorization safety study was consistent with results from previous studies showing that exposure to PLEGRIDY or AVONEX during pregnancy or lactation did not negatively impact child development or intrauterine growth. Further, a preliminary analysis of the German Multiple Sclerosis and Pregnancy Registry assessed child development in infants born to mothers with AVONEX or PLEGRIDY exposure during pregnancy, and treatment did not negatively impact children’s development. Title and Times of Data Presentations Featured at ECTRIMS: Natalizumab-Treated RRMS Patients with Prior DMT Use Report Better Outcomes, Treatment Satisfaction and Unique Benefits Than Similar Patients Treated with Ocrelizumab – EP0851 – October 26, 8 a.m. CET / 2 a.m. ET Disease Activity and Pregnancy Outcomes After Long-Term Exposure to Natalizumab During Pregnancy – 0039 – October 26, 2:56 p.m. CET / 8:56 a.m. ET SISTER – Subcutaneous: Non-Interventional, Observational, Prospective, German Multicentre, Open Label Study Over 12-Months for TYSABRI Patient Preference – Experience from Real-World – Preliminary Results of the 1st Interim Analysis – P365 – October 26, 8 a.m. CET / 2 a.m. ET Long-Term Effectiveness of Natalizumab for RRMS: Dutch and Global Interim Results from TYSABRI Observational Program – P373 – October 26, 8 a.m. CET / 2 a.m. ET Exploratory Magnetic Resonance Imaging Endpoints from NOVA: A Randomized Controlled Study of the Efficacy of 6-Week Dosing of Natalizumab vs Continued 4-Week Treatment for Multiple Sclerosis – P350 – October 26, 8 a.m. CET / 2 a.m. ET Interferon- or Peginterferon-Beta 1a Exposure During Pregnancy in Women with Multiple Sclerosis: Outcomes on Child Development – P075 – October 26, 8 a.m. CET / 2 a.m. ET and October 27, 1:05 p.m. CET / 7:05 a.m. ET StratifyJCV™ Serum Anti-JCV Antibody Assay for Natalizumab Patients: Unilabs Global Cohort Data Descriptive Analysis and Unilabs Customer Satisfaction Survey Results – P750 – October 26, 8 a.m. CET / 2 a.m. ET Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis – P708 – October 26, 8 a.m. CET / 2 a.m. ET Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Final Safety and Efficacy Results from the Phase 3 EVOLVE-MS-1 Study – P712 – October 26, 8 a.m. CET / 2 a.m. ET Interferon-Beta Exposure During Pregnancy and Breastfeeding: Impact on Birth Outcome and Child Development – Results from the Post-Authorisation Safety Study PRIMA – P478 – October 26, 8 a.m. CET / 2 a.m. ET Multi-Center, Randomized, Double-Blinded Assessment of Dimethyl Fumarate in Extending the Time to a First Clinical Demyelinating Event in Radiologically Isolated Syndrome (ARISE) – 0179 – October 28, 3:49 p.m. CET / 9:49 a.m. ET About VUMERITY® (diroximel fumarate) VUMERITY is an oral fumarate approved in the U.S. for the treatment of relapsing forms of multiple sclerosis in adults, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. Once in the body, VUMERITY rapidly converts to monomethyl fumarate, the same active metabolite of dimethyl fumarate (TECFIDERA). VUMERITY is available in 15 countries, and more than 28,200 patients have been treated with it, representing more than 24,200 patient-years of exposure across clinical trial use and patients prescribed VUMERITY.2 VUMERITY is contraindicated in patients with a known hypersensitivity to diroximel fumarate, dimethyl fumarate or any of the excipients of VUMERITY and in patients taking dimethyl fumarate. VUMERITY can cause anaphylaxis and angioedema after the first dose or at any time during treatment. PML has occurred in patients with MS treated with dimethyl fumarate (which has the same active metabolite as VUMERITY). PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received dimethyl fumarate for four years while enrolled in a clinical trial. Serious cases of herpes zoster have occurred with dimethyl fumarate, including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Other serious opportunistic infections have occurred with dimethyl fumarate, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. VUMERITY may decrease lymphocyte counts. In the MS placebo-controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with dimethyl fumarate and then remained stable. Four weeks after stopping dimethyl fumarate, mean lymphocyte counts increased but did not return to baseline. Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate in the post-marketing setting. The onset has ranged from a few days to several months after initiation of treatment. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than five-fold the upper limit of normal and elevation of total bilirubin to greater than two-fold the upper limit of normal have been observed. VUMERITY may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). Forty percent of patients taking dimethyl fumarate reported flushing, which was mostly mild to moderate in severity. Three percent of patients discontinued dimethyl fumarate for flushing and <1% had serious flushing events that led to hospitalization. The most common adverse events associated with dimethyl fumarate (incidence ≥10% and ≥2% more than placebo) were flushing, abdominal pain, diarrhea and nausea. A list of adverse events can be found in the full VUMERITY product labeling for each country where it is approved. Please click here for Important Safety Information and full Prescribing Information, including Patient Information for VUMERITY in the U.S., or visit your respective country’s product website. About TECFIDERA® (dimethyl fumarate) TECFIDERA is approved for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. TECFIDERA has been shown to reduce the rate of MS relapses, slow the progression of disability and impact the number of MS brain lesions, while demonstrating a well-characterized safety pro people with relapsing forms of MS. TECFIDERA is approved in 69 countries, and more than 580,500 patients have been treated with it, representing more than 1.2 million patient-years of exposure across clinical trial use and patients prescribed TECFIDERA.3 TECFIDERA is contraindicated in patients with a known hypersensitivity to dimethyl fumarate or any of the excipients of TECFIDERA. TECFIDERA can cause anaphylaxis and angioedema after the first dose or at any time during treatment. PML has occurred in patients with MS treated with TECFIDERA. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received TECFIDERA for four years while enrolled in a clinical trial. Serious cases of herpes zoster have occurred with TECFIDERA, including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Other serious opportunistic infections have occurred with TECFIDERA, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. TECFIDERA may decrease lymphocyte counts. In the MS placebo-controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment with TECFIDERA and then remained stable. Four weeks after stopping TECFIDERA, mean lymphocyte counts increased but did not return to baseline. Clinically significant cases of liver injury have been reported in patients treated with TECFIDERA in the post-marketing setting. The onset has ranged from a few days to several months after initiation of treatment. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than five-fold the upper limit of normal and elevation of total bilirubin to greater than two-fold the upper limit of normal have been observed. TECFIDERA may cause flushing (e.g. warmth, redness, itching, and/or burning sensation). Forty percent of patients taking TECFIDERA reported flushing, which was mostly mild to moderate in severity. Three percent of patients discontinued TECFIDERA for flushing and <1% had serious flushing events that led to hospitalization. The most common adverse events associated with TECFIDERA (incidence ≥10% and ≥2% more than placebo) were flushing, abdominal pain, diarrhea and nausea. A list of adverse events can be found in the full TECFIDERA product labeling for each country where it is approved. Please click here for Important Safety Information and full Prescribing Information, including Patient Information for TECFIDERA in the U.S., or visit your respective country’s product website. About TYSABRI® (natalizumab) TYSABRI is approved in the U.S. as monotherapy for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML). When initiating and continuing treatment with TYSABRI, physicians should consider whether the expected benefit of TYSABRI is sufficient to offset this risk. TYSABRI is approved in more than 80 countries, and over 248,000 people worldwide have been treated with TYSABRI, with more than 1 million patient-years of experience, based on clinical trials and prescription data.1 TYSABRI increases the risk of PML, a rare opportunistic viral infection of the brain which has been associated with death or severe disability. Risk factors that increase the risk of PML are the presence of anti-JC virus antibodies, prior immunosuppressant use and longer TYSABRI treatment duration. Patients who have all three risk factors have the highest risk of developing PML. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. TYSABRI is contraindicated in patients who have or have had PML and in patients who have had a hypersensitivity reaction to TYSABRI. TYSABRI also increases the risk of developing encephalitis and meningitis caused by herpes simplex and varicella zoster viruses, and serious, life-threatening and sometimes fatal cases have been reported in the post-marketing setting in MS patients receiving TYSABRI. Clinically significant liver injury, including acute liver failure requiring transplant, has also been reported in the post-marketing setting. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses. Hypersensitivity reactions have occurred in patients receiving TYSABRI, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%. The immune system effects of TYSABRI may increase the risk for infections. In Study MS1, certain types of infections—including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections—occurred more often in TYSABRI-treated patients than in placebo-treated patients. In clinical trials, TYSABRI was observed to induce increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persisted during TYSABRI exposure, but were reversible, returning to baseline levels usually within 16 weeks after the last dose. Cases of thrombocytopenia, including immune thrombocytopenic purpura, have been reported with the use of TYSABRI in the post-marketing setting. Cases of neonatal thrombocytopenia, at times associated with anemia, have been reported in newborns with in utero exposure to TYSABRI. The most common adverse reactions associated with TYSABRI (incidence ≥10% and ≥2% more than placebo) were headache, fatigue, infusion reactions, urinary tract infections, arthralgia, depression, pain in extremity, rash, gastroenteritis, and vaginitis. A list of adverse events can be found in the full TYSABRI product labeling for each country where it is approved. Please click here for Important Safety Information, including Boxed Warning, and full Prescribing Information, including Medication Guide for TYSABRI in the U.S., or visit your respective country’s product website. About PLEGRIDY® (peginterferon beta-1a) PLEGRIDY (peginterferon beta-1a) is indicated for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. PLEGRIDY is currently approved in over 60 countries including the U.S., Canada, Australia and Switzerland and across the European Union. Over 81,000 people worldwide have been treated with PLEGRIDY, with over 170,000 patient-years of experience, based on prescription data.4 Biogen continues to work toward making PLEGRIDY available in additional countries across the globe. PLEGRIDY is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation. Rare cases of severe hepatic injury, including cases of hepatic failure have been reported in patients taking PLEGRIDY. Symptoms of depression, suicidal ideation or psychosis, and cases of suicide, have been reported with increased frequency with patients receiving PLEGRIDY. Serious allergic reactions are rare complications of interferon beta; anaphylaxis has been reported with use of PLEGRIDY. Injection site reactions, including injection site necrosis, can occur with the use of interferon beta, including PLEGRIDY; injection site abscesses and cellulitis have been reported in the post-marketing setting with use of PLEGRIDY. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics. Cases of congestive heart failure, cardiomyopathy and cardiomyopathy with congestive heart failure have been reported in patients without known predisposition. Decreased peripheral blood counts have been reported from post-marketing experience; monitor patients for infections, bleeding and anemia; monitor complete blood cell counts, differential white cell counts, and platelet counts. Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported several weeks to years after starting interferon beta products. Autoimmune disorders of multiple target organs including idiopathic thrombocytopenia, hyper- and hypothyroidism, and autoimmune hepatitis have been reported. Seizures have been reported in patients using PLEGRIDY. The most common adverse reactions in clinical trials of subcutaneous PLEGRIDY (incidence ≥10% and at least 2% more frequent on PLEGRIDY than on placebo) were injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia. A list of adverse events can be found in the full PLEGRIDY product labeling for each country where it is approved. Please click here for Important Safety Information and full Prescribing Information, including Medication Guide for PLEGRIDY in the U.S., or visit your respective country’s product website. About AVONEX® (interferon beta-1a) AVONEX is indicated for the treatment of relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. AVONEX is approved in over 90 countries and over 625,000 people worldwide have been treated with AVONEX, with over 2.8 million patient-years of experience, based on prescription data.5 Avonex is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, or any other component of the formulation. Symptoms of depression, suicidal ideation or psychosis, and cases of suicide, have been reported with increased frequency with patients receiving AVONEX. Rare cases of severe hepatic injury, including cases of hepatic failure have been reported in patients taking AVONEX. Anaphylaxis has been reported as a rare complication of AVONEX use; other allergic reactions have included dyspnea, orolingual edema, skin rash and urticaria. Injection site reactions, including injection site necrosis, can occur with the use of interferon beta, including AVONEX. Injection site abscesses and cellulitis and injection site necrosis have been reported in the post-marketing setting with use of AVONEX. Some cases required treatment with hospitalization for surgical drainage and intravenous antibiotics. Cases of congestive heart failure, cardiomyopathy and cardiomyopathy with congestive heart failure have been reported in patients without known predisposition. Decreased peripheral blood counts have been reported from post-marketing experience. Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported several weeks to years after starting interferon beta products. Seizures have been temporally associated with the use of beta interferons in clinical trials and post-marketing safety surveillance. Post-marketing reports of autoimmune disorders of multiple target organs in AVONEX-treated patients including idiopathic thrombocytopenia, hyper- and hypothyroidism, and rare cases of autoimmune hepatitis. Routine periodic blood chemistry, hematology, liver function and thyroid function tests are recommended. The most commonly reported adverse reactions (at least 5% more frequent on AVONEX than on placebo) were flu-like symptoms. A list of adverse events can be found in the full AVONEX product labeling for each country where it is approved. Please click here for Important Safety Information and full Prescribing Information, including Medication Guide for AVONEX in the U.S., or visit your respective country’s product website. About Biogen As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need. In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities. We routinely post information that may be important to investors on our website at . Follow us on social media - Twitter, LinkedIn, Facebook, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to the potential benefits, safety and efficacy of TYSABRI and VUMERITY; the results of certain real-world data; clinical trials and data readouts and presentations; the identification and treatment of MS; our research and development program for the treatment of MS; and the potential of our commercial business, including TYSABRI and VUMERITY. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis; risks of unexpected costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise. References: Combined post-marketing data based on prescriptions and clinical trials exposure to TYSABRI as of July 31, 2022. TYSABRI subcutaneous administration exposure as of September 30, 2022. Combined post-marketing data based on prescriptions and clinical trials exposure to VUMERITY as of June 30, 2022. Combined post-marketing data based on prescriptions and clinical trials exposure to TECFIDERA as of June 30, 2022. Post-marketing data based on PLEGRIDY prescriptions as of June 30, 2022. Post-marketing data based on AVONEX prescriptions as of June 30, 2022. MEDIA CONTACT: Allison Parks + 1 248 229 4461 public.affairs@biogen.com INVESTOR CONTACT: Mike Hencke +1 781 464 2442 IR@biogen.com

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: