Cladribine

DARMSTADT, Germany--(BUSINESS WIRE)--Not intended for UK-, US- or Canada-based media Merck, a leading science and technology company, today announced the presentation of over 30 abstracts from its multiple sclerosis (MS) portfolio. New four-year data from two large Phase 4 studies highlight the long-term efficacy, favorable disability outcomes and durable impact of MAVENCLAD® (cladribine tablets) in people living with relapsing multiple sclerosis (RMS). These findings are to be presented at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held September 24-26 in Barcelona. “As the only high-efficacy short-course oral treatment, MAVENCLAD has demonstrated sustained benefits across a variety of outcomes—extending beyond relapses and MRI—without requiring continuous immunosuppression,” said Alex Kulla, Senior Vice President & Global Head of the Neurology & Immunology Medical Unit for the Healthcare business of Merck. “With over two decades of clinical experience and substantial real-world data, MAVENCLAD has been utilized to treat more than 130,000 individuals, amounting to over 360,000 patient-years of exposure. The comprehensive data presented at ECTRIMS 2025 reinforces its role in delivering durable, effective care for individuals with RMS—supporting them from early diagnosis through later stages of life.” Key MAVENCLAD data: An integrated analysis of four-year data from CLARIFY-MS (n=482) and MAGNIFY-MS (n=270), including their extension studies, showed low rates of disability accumulation and progression independent of relapse activity (PIRA) in patients treated with MAVENCLAD, especially those who initiated treatment in the early stages of their disease. At Year 4, 83.4% of patients were free from confirmed disability progression (CDP) and 89.2% were free from PIRA. 15.4% experienced confirmed disability improvement (CDI). Patients aged ≤40 experienced lower rates of PIRA compared to those over 40 (7.6% vs. 15.4%, respectively). The analysis demonstrated that MAVENCLAD provided durable efficacy after short-course treatment, with long-term control over both inflammatory and non-inflammatory components of MS-related disability. At Year 4, 83.4% of patients were free from confirmed disability progression (CDP) and 89.2% were free from PIRA. 15.4% experienced confirmed disability improvement (CDI). Patients aged ≤40 experienced lower rates of PIRA compared to those over 40 (7.6% vs. 15.4%, respectively). The analysis demonstrated that MAVENCLAD provided durable efficacy after short-course treatment, with long-term control over both inflammatory and non-inflammatory components of MS-related disability. Data from MAGNIFY-MS showed MAVENCLAD reduced serum and cerebrospinal fluid (CSF) biomarkers of neuroinflammation, suggesting a broader central nervous system (CNS) benefit. At Year 2, reductions were observed in key biomarkers, including serum glial fibrillary acidic protein (GFAP), immunoglobulin G (IgG) index, and C-X-C motif chemokine ligand 13 (CXCL-13) levels. At Year 2, reductions were observed in key biomarkers, including serum glial fibrillary acidic protein (GFAP), immunoglobulin G (IgG) index, and C-X-C motif chemokine ligand 13 (CXCL-13) levels. Brain imaging data from MAGNIFY-MS indicated that the brain atrophy rate in MAVENCLAD-treated patients was comparable to that observed in the healthy population, reinforcing the importance of brain volume (BV) preservation as a therapeutic goal in MS. From Years 2 to 4, annualized percent BV change remained below 0.4%, across all subgroups. Patients with low brain atrophy rates at Year 4 had markedly lower annualized relapse rate (ARR) (0.04 ±0.12 vs. 0.16 ±0.26) and less clinical deterioration compared to those with annualized percentage BV change exceeding -0.4%. From Years 2 to 4, annualized percent BV change remained below 0.4%, across all subgroups. Patients with low brain atrophy rates at Year 4 had markedly lower annualized relapse rate (ARR) (0.04 ±0.12 vs. 0.16 ±0.26) and less clinical deterioration compared to those with annualized percentage BV change exceeding -0.4%. Additional MAVENCLAD presentations: Poster Presentation Title: Treatment Continuation With Cladribine Tablets Beyond Year 4: Analysis of Longitudinal Prescription Data From Germany Lead Author: David Kormann, Real World Data Analytics, IQVIA Commercial GmbH & Co. OHG, Frankfurt, Germany Lead Author: David Kormann, Real World Data Analytics, IQVIA Commercial GmbH & Co. OHG, Frankfurt, Germany Poster Presentation Title: Treatment continuation with cladribine tablets (CladT) beyond year 4– second interim analysis of the CLIP-5 study Lead Author: Catharina Korsukewitz, University Hospital Muenster, Muenster, Germany Lead Author: Catharina Korsukewitz, University Hospital Muenster, Muenster, Germany Poster Presentation Title: Incidence Rate of Malignancies in People with Multiple Sclerosis Newly Initiating Cladribine Tablets or Fingolimod: Second Interim Results from CLARION Lead Author: Anna Glaser, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Lead Author: Anna Glaser, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Poster Presentation Title: Clinical Outcomes of Cladribine Tablets in Aging (≥50 years) Patients with Relapsing Multiple Sclerosis in a Real-World Setting: Insights From the ‘Aging’ Study Lead Author: Joshua Katz, Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, MA, United States Lead Author: Joshua Katz, Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, MA, United States Below is the full list of MAVENCLAD abstracts accepted for presentation at ECTRIMS 2025: The Effect of Cladribine Tablets on Brain Volume over 4 Years in the MAGNIFY-MS Extension Study Barkhof F, Schmierer K, Vermersch P, et al. Poster: P687 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Barkhof F Impact of Cladribine Tablets on GFAP Levels and Intrathecal Biomarkers in RMS: Results from the MAGNIFY-MS Study Wiendl H, Derfuss T, Sponton L, et al. Poster: P1694 Session: ePoster Date: September 24-26, 2025 Presenter: Wiendl H Long-Term Effect of Cladribine Tablets on Disability Progression and Improvement: Insights from Pooled Analyses of CLARIFY-MS and MAGNIFY-MS Studies Vermersch P, Wiendl H, Leocani L, et al. Poster: P335 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Vermersch P Cladribine Tablets Show Low 4-Year PIRA Rates in MS: Insights from Pooled Analyses of CLARIFY-MS and MAGNIFY-MS Studies Montalban X, De Stefano N, Hodgkinson S, et al. Poster: P1707 Session: ePoster Date: September 24-26, 2025 Presenter: Montalban X Comparing Changes in Brain Tissue Damage Between the Two-year Active Dosing Treatment Period and the Following Two Years Extension Period in Cladribine-treated MS Patients Stratified by MRI Phenotypes De Stefano N, Sforazzini F, Luchetti L, et al. Poster: P208 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: De Stefano N Cladribine Tablets-treated Multiple Sclerosis Patients Show Different Spatio-temporal Patterns of Acute, Chronic and Resolving Brain Inflammatory Activity Gentile G, Smyk A, Ben-Amor A-F, et al. Poster: P1450 Session: ePoster Date: September 24-26, 2025 Presenter: Gentile G Using Deep Learning on Baseline MRI Data for Highly Accurate Prediction of Cladribine Tablets-treated MS Patients who Improve Physical and Cognitive Disability in 4 Years Battaglini M, Sforazzini F, Luchetti L, et al. Poster: P672 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Battaglini M Incidence Rate of Malignancies in People with Multiple Sclerosis Newly Initiating Cladribine Tablets or Fingolimod: Second Interim Results from CLARION Glaser A, Ziemssen T, Butzkueven H, et al. Poster: P856 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Glaser A Real-world Experience with Cladribine (Mavenclad) in the MSBase Registry 2025 Spelman T, van der Walt A, Ozakbas S, et al. Poster: P875 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Butzkueven H Treatment Continuation With Cladribine Tablets Beyond Year 4: Analysis of Longitudinal Prescription Data From Germany Kormann D, Parekh M, von der Maßen K, et al. Poster: P1773 Session: ePoster Date: September 24-26, 2025 Presenter: Kormann D Real-world Experience with Cladribine Tablets in Older Age Groups in the MSBase Registry Spelman T, van der Walt A, Havrdova E, et al. Poster: P1985 Session: ePoster Date: September 24-26, 2025 Presenter: Butzkueven H Cladribine Tablets Reduce Pathological Brain Ageing Gap in MS Patients Leoncini M, Battaglini M, Sforazzini F, et al. Poster: P432 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Leoncini M Clinical Outcomes of Cladribine Tablets in Aging (≥50 years) Patients with Relapsing Multiple Sclerosis in a Real-World Setting: Insights From the ‘Aging’ Study Katz J, Hughes B, Gutierrez A, et al. Poster: P332 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Katz J Relationship Between CSF Cellular Populations and MRI Biomarkers of MS Disease Severity: Insights from the CLOCK-MS Study Samara A, Judge B, Salter A, et al. Poster: P1471 Session: ePoster Date: September 24-26, 2025 Presenter: Brier MR Three-Year Effectiveness and Safety Data for Cladribine Tablets in Patients with Relapsing Multiple Sclerosis after Transitioning from Natalizumab (CLADRINA Study) Sguigna P, Okai A, Kaplan J, et al. Poster: P1947 Session: ePoster Date: September 24-26, 2025 Presenter: Sguigna P Treatment Continuation with Cladribine Tablets (CladT) Beyond Year 4– Second Interim Analysis of the CLIP-5 Study Korsukewitz C, Richter N, Klehmet J, et al. Poster: P1803 Session: ePoster Date: September 24-26, 2025 Presenter: Korsukewitz C Long-term Effects of Treatment with Cladribine Tablets on Cognition and Treatment Satisfaction in People with Relapsing Multiple Sclerosis: 4‑year Results from the Noninterventional CLADQoL Study Penner I-K, Chudecka A, Refik P, et al. Poster: P1820 Session: ePoster Date: September 24-26, 2025 Presenter: Penner I-K 48 Month Follow-up of Maven4: a Phase IV Non-interventional, Prospective, Spanish Multicenter Study to Assess the Long Term Effectiveness of Cladribine Tablets in Real-world Clinical Practice Aladro-Benito Y, Costa-Frossard L, Sánchez Magro MI, et al. Poster: P346 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Aladro-Benito Y Design and Baseline Characteristics of the Real-world MAVENAGE Study in Relapsing MS Patients Older and Younger Than 50 Years Treated with Cladribine Tablets Meca-Lallana JE, Eichau S, Oreja-Guevara C, Meca V, et al. Poster: P1649 Session: ePoster Date: September 24-26, 2025 Presenter: Meca-Lallana JE Retrospective Analysis of Multiple Sclerosis Patients Who Initiated Oral Cladribine 5-8 Years Ago – Data from a German Cladribine Cohort Woitschach L, Cepek L, Kowarik M, et al. Poster: P357 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Ernst M Clinical Effectiveness of Cladribine Tablets for PwMS Switching from Natalizumab, AntiCD20 Treatment or “Other”; Data from the Swedish Post-market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Forsberg L, Larsson V, Hillert J, et al. Poster: P1762 Session: ePoster Date: September 24-26, 2025 Presenter: Forsberg L Clinical Effectiveness and Safety of Cladribine Tablets for PwMS Treated at Least 36 Months in the Swedish Post-market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Forsberg L, Larsson V, Hillert J, et al. Poster: P344 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Forsberg L Clinical Effectiveness of Cladribine Tablets for Patients Below or Above 50 Years of Age at Treatment Start in the Swedish Post-market Surveillance Study "Immunomodulation and Multiple Sclerosis Epidemiology 10" (IMSE 10) Larsson V, Forsberg L, Hillert J, et al. Poster: P861 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Larsson V CLADCOMS - CLADribine Tablets Long-term Control of MS – a Post-Marketing Investigator Driven Study Larsson V, Forsberg L, Nilsson P, et al. Poster: P865 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Larsson V Clinical Effectiveness of Cladribine Tablets for Patients with Few vs Many Treatments Prior CladT Initiation in the CLADCOMS Study -CLADribine Tablets Long-term Control Of MS – a Post-marketing Investigator Driven Study Larsson V, Forsberg L, Nilsson P, et al. Poster: P1804 Session: ePoster Date: September 24-26, 2025 Presenter: Larsson V Recurrent Effects on the Clonal Composition of Peripheral B Cells in MS Patients During the Second Year of Cladribine Treatment Tieck MP, Vasilenko N, Stadelmaier J, et al. Poster: P813 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Tieck MP Preliminary Data of Paramagnetic Rim Lesion Dynamic at 7 Tesla Magnetic Resonance Imaging in Cladribine Tablets-Treated People with Multiple Sclerosis Dal-Bianco A, Hametner S, Grabner G, et al. Poster: P216 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Dal-Bianco A Baseline and Early Safety Data Following Full Recruitment of ChariotMS, the First DMT trial for People with Advanced MS (EDSS 6.5-8.5) Schmierer K, Mattoscio M, De Angelis F, et al. Poster: P1633 Session: ePoster Date: September 24-26, 2025 Presenter: Schmierer K Breaking Inflammatory Cycles: Cladribine Targets Pathogenic B Cell Subsets in Multiple Sclerosis Pirronello M, Picozza M, Corbisiero S, et al. Poster: P1374 Session: ePoster Date: September 24-26, 2025 Presenter: Battistini L Circulating MicroRNAs as Potential Biomarkers for Treatment Response in Cladribine-Treated Multiple Sclerosis Patients Vigiser I, Zeevi Y, Piura Y, Kolb H, Golan M, Karni A, Regev K Poster: P762 Session: ePoster Date: September 24-26, 2025 Presenter: Vigiser I Integrin β1 Demarks Circulating Precursors of Brain-residing Antibody-secreting Cells in People with MS Kuiper K, Bogers L, Rip J, et al. Oral presentation: O123 Session: Scientific Session 14: Antibody-mediated pathology Date: September 26, 2025 Time: 12:26-12:33 am PDT/03:26-03:33 am EDT Presenter: Smolders J Early Lymphocyte Reduction as a Potential Marker of Cladribine Efficacy Celius E, et al. Poster: P2028 Session: ePoster Date: September 24-26, 2025 Presenter: Celius E 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. More than 130,000 patients have been treated with MAVENCLAD since its launch in 2019. MAVENCLAD has been approved in over 80 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit www.MAVENCLAD.com for more 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 2.9 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. Merck in Neurology and Immunology Merck has a long-standing legacy in neurology and immunology, with significant R&D and commercial experience in multiple sclerosis (MS). The company’s current MS portfolio includes two products for the treatment of relapsing MS – Rebif® (interferon beta-1a) and MAVENCLAD® (cladribine tablets). Merck aims to improve the lives of patients by addressing areas of unmet medical needs. In addition to Merck’s commitment to MS, the company also has a pipeline focusing on discovering new therapies that have potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE) and generalized myasthenia gravis (gMG). About Merck Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 62,000 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 providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2024, Merck generated sales of € 21.2 billion in 65 countries. Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics. All Merck press releases are distributed by e-mail at the same time they become available on the Merck website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

BOSTON--(BUSINESS WIRE)--EMD Serono, the Healthcare business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced the presentation of over 30 abstracts from its multiple sclerosis (MS) portfolio. New four-year data from two large Phase 4 studies highlight the long-term efficacy, favorable disability outcomes and durable impact of MAVENCLAD® (cladribine) tablets in people living with relapsing multiple sclerosis (RMS). These findings are to be presented at the 41st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held September 24-26 in Barcelona. “As the only high-efficacy short-course oral treatment, MAVENCLAD has demonstrated sustained benefits across a variety of outcomes—extending beyond relapses and MRI—without requiring continuous immunosuppression,” said Alex Kulla, Senior Vice President & Global Head of the Neurology & Immunology Medical Unit for the Healthcare business of Merck KGaA, Darmstadt, Germany. “With over two decades of clinical experience and substantial real-world data, MAVENCLAD has been utilized to treat more than 130,000 individuals, amounting to over 360,000 patient-years of exposure. The comprehensive data presented at ECTRIMS 2025 reinforces its role in delivering durable, effective care for individuals with RMS—supporting them from early diagnosis through later stages of life.” Key MAVENCLAD data: An integrated analysis of four-year data from CLARIFY-MS (n=482) and MAGNIFY-MS (n=270), including their extension studies, showed low rates of disability accumulation and progression independent of relapse activity (PIRA) in patients treated with MAVENCLAD, especially those who initiated treatment in the early stages of their disease. At Year 4, 83.4% of patients were free from confirmed disability progression (CDP) and 89.2% were free from PIRA. 15.4% experienced confirmed disability improvement (CDI). Patients aged ≤40 experienced lower rates of PIRA compared to those over 40 (7.6% vs. 15.4%, respectively). The analysis demonstrated that MAVENCLAD provided durable efficacy after short-course treatment, with long-term control over both inflammatory and non-inflammatory components of MS-related disability. At Year 4, 83.4% of patients were free from confirmed disability progression (CDP) and 89.2% were free from PIRA. 15.4% experienced confirmed disability improvement (CDI). Patients aged ≤40 experienced lower rates of PIRA compared to those over 40 (7.6% vs. 15.4%, respectively). The analysis demonstrated that MAVENCLAD provided durable efficacy after short-course treatment, with long-term control over both inflammatory and non-inflammatory components of MS-related disability. Data from MAGNIFY-MS showed MAVENCLAD reduced serum and cerebrospinal fluid (CSF) biomarkers of neuroinflammation, suggesting a broader central nervous system (CNS) benefit. At Year 2, reductions were observed in key biomarkers, including serum glial fibrillary acidic protein (GFAP), immunoglobulin G (IgG) index, and C-X-C motif chemokine ligand 13 (CXCL-13) levels. At Year 2, reductions were observed in key biomarkers, including serum glial fibrillary acidic protein (GFAP), immunoglobulin G (IgG) index, and C-X-C motif chemokine ligand 13 (CXCL-13) levels. Brain imaging data from MAGNIFY-MS indicated that the brain atrophy rate in MAVENCLAD-treated patients was comparable to that observed in the healthy population, reinforcing the importance of brain volume (BV) preservation as a therapeutic goal in MS. From Years 2 to 4, annualized percent BV change remained below 0.4%, across all subgroups. Patients with low brain atrophy rates at Year 4 had markedly lower annualized relapse rate (ARR) (0.04 ±0.12 vs. 0.16 ±0.26) and less clinical deterioration compared to those with annualized percentage BV change exceeding -0.4%. From Years 2 to 4, annualized percent BV change remained below 0.4%, across all subgroups. Patients with low brain atrophy rates at Year 4 had markedly lower annualized relapse rate (ARR) (0.04 ±0.12 vs. 0.16 ±0.26) and less clinical deterioration compared to those with annualized percentage BV change exceeding -0.4%. Additional MAVENCLAD presentations: Poster Presentation Title: Treatment Continuation With Cladribine Tablets Beyond Year 4: Analysis of Longitudinal Prescription Data From Germany Lead Author: David Kormann, Real World Data Analytics, IQVIA Commercial GmbH & Co. OHG, Frankfurt, Germany Lead Author: David Kormann, Real World Data Analytics, IQVIA Commercial GmbH & Co. OHG, Frankfurt, Germany Poster Presentation Title: Treatment continuation with cladribine tablets (CladT) beyond year 4– second interim analysis of the CLIP-5 study Lead Author: Catharina Korsukewitz, University Hospital Muenster, Muenster, Germany Lead Author: Catharina Korsukewitz, University Hospital Muenster, Muenster, Germany Poster Presentation Title: Incidence Rate of Malignancies in People with Multiple Sclerosis Newly Initiating Cladribine Tablets or Fingolimod: Second Interim Results from CLARION Lead Author: Anna Glaser, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Lead Author: Anna Glaser, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Poster Presentation Title: Clinical Outcomes of Cladribine Tablets in Aging (≥50 years) Patients with Relapsing Multiple Sclerosis in a Real-World Setting: Insights From the ‘Aging’ Study Lead Author: Joshua Katz, Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, MA, United States Lead Author: Joshua Katz, Elliot Lewis Center for Multiple Sclerosis Care, Wellesley, MA, United States Below is the full list of MAVENCLAD abstracts accepted for presentation at ECTRIMS 2025: The Effect of Cladribine Tablets on Brain Volume over 4 Years in the MAGNIFY-MS Extension Study Barkhof F, Schmierer K, Vermersch P, et al. Poster: P687 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Barkhof F Impact of Cladribine Tablets on GFAP Levels and Intrathecal Biomarkers in RMS: Results from the MAGNIFY-MS Study Wiendl H, Derfuss T, Sponton L, et al. Poster: P1694 Session: ePoster Date: September 24-26, 2025 Presenter: Wiendl H Long-Term Effect of Cladribine Tablets on Disability Progression and Improvement: Insights from Pooled Analyses of CLARIFY-MS and MAGNIFY-MS Studies Vermersch P, Wiendl H, Leocani L, et al. Poster: P335 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Vermersch P Cladribine Tablets Show Low 4-Year PIRA Rates in MS: Insights from Pooled Analyses of CLARIFY-MS and MAGNIFY-MS Studies Montalban X, De Stefano N, Hodgkinson S, et al. Poster: P1707 Session: ePoster Date: September 24-26, 2025 Presenter: Montalban X Comparing Changes in Brain Tissue Damage Between the Two-year Active Dosing Treatment Period and the Following Two Years Extension Period in Cladribine-treated MS Patients Stratified by MRI Phenotypes De Stefano N, Sforazzini F, Luchetti L, et al. Poster: P208 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: De Stefano N Cladribine Tablets-treated Multiple Sclerosis Patients Show Different Spatio-temporal Patterns of Acute, Chronic and Resolving Brain Inflammatory Activity Gentile G, Smyk A, Ben-Amor A-F, et al. Poster: P1450 Session: ePoster Date: September 24-26, 2025 Presenter: Gentile G Using Deep Learning on Baseline MRI Data for Highly Accurate Prediction of Cladribine Tablets-treated MS Patients who Improve Physical and Cognitive Disability in 4 Years Battaglini M, Sforazzini F, Luchetti L, et al. Poster: P672 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Battaglini M Incidence Rate of Malignancies in People with Multiple Sclerosis Newly Initiating Cladribine Tablets or Fingolimod: Second Interim Results from CLARION Glaser A, Ziemssen T, Butzkueven H, et al. Poster: P856 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Glaser A Real-world Experience with Cladribine (Mavenclad) in the MSBase Registry 2025 Spelman T, van der Walt A, Ozakbas S, et al. Poster: P875 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Butzkueven H Treatment Continuation With Cladribine Tablets Beyond Year 4: Analysis of Longitudinal Prescription Data From Germany Kormann D, Parekh M, von der Maßen K, et al. Poster: P1773 Session: ePoster Date: September 24-26, 2025 Presenter: Kormann D Real-world Experience with Cladribine Tablets in Older Age Groups in the MSBase Registry Spelman T, van der Walt A, Havrdova E, et al. Poster: P1985 Session: ePoster Date: September 24-26, 2025 Presenter: Butzkueven H Cladribine Tablets Reduce Pathological Brain Ageing Gap in MS Patients Leoncini M, Battaglini M, Sforazzini F, et al. Poster: P432 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Leoncini M Clinical Outcomes of Cladribine Tablets in Aging (≥50 years) Patients with Relapsing Multiple Sclerosis in a Real-World Setting: Insights From the ‘Aging’ Study Katz J, Hughes B, Gutierrez A, et al. Poster: P332 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Katz J Relationship Between CSF Cellular Populations and MRI Biomarkers of MS Disease Severity: Insights from the CLOCK-MS Study Samara A, Judge B, Salter A, et al. Poster: P1471 Session: ePoster Date: September 24-26, 2025 Presenter: Brier MR Three-Year Effectiveness and Safety Data for Cladribine Tablets in Patients with Relapsing Multiple Sclerosis after Transitioning from Natalizumab (CLADRINA Study) Sguigna P, Okai A, Kaplan J, et al. Poster: P1947 Session: ePoster Date: September 24-26, 2025 Presenter: Sguigna P Treatment Continuation with Cladribine Tablets (CladT) Beyond Year 4– Second Interim Analysis of the CLIP-5 Study Korsukewitz C, Richter N, Klehmet J, et al. Poster: P1803 Session: ePoster Date: September 24-26, 2025 Presenter: Korsukewitz C Long-term Effects of Treatment with Cladribine Tablets on Cognition and Treatment Satisfaction in People with Relapsing Multiple Sclerosis: 4‑year Results from the Noninterventional CLADQoL Study Penner I-K, Chudecka A, Refik P, et al. Poster: P1820 Session: ePoster Date: September 24-26, 2025 Presenter: Penner I-K 48 Month Follow-up of Maven4: a Phase IV Non-interventional, Prospective, Spanish Multicenter Study to Assess the Long Term Effectiveness of Cladribine Tablets in Real-world Clinical Practice Aladro-Benito Y, Costa-Frossard L, Sánchez Magro MI, et al. Poster: P346 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Aladro-Benito Y Design and Baseline Characteristics of the Real-world MAVENAGE Study in Relapsing MS Patients Older and Younger Than 50 Years Treated with Cladribine Tablets Meca-Lallana JE, Eichau S, Oreja-Guevara C, Meca V, et al. Poster: P1649 Session: ePoster Date: September 24-26, 2025 Presenter: Meca-Lallana JE Retrospective Analysis of Multiple Sclerosis Patients Who Initiated Oral Cladribine 5-8 Years Ago – Data from a German Cladribine Cohort Woitschach L, Cepek L, Kowarik M, et al. Poster: P357 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Ernst M Clinical Effectiveness of Cladribine Tablets for PwMS Switching from Natalizumab, AntiCD20 Treatment or “Other”; Data from the Swedish Post-market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Forsberg L, Larsson V, Hillert J, et al. Poster: P1762 Session: ePoster Date: September 24-26, 2025 Presenter: Forsberg L Clinical Effectiveness and Safety of Cladribine Tablets for PwMS Treated at Least 36 Months in the Swedish Post-market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Forsberg L, Larsson V, Hillert J, et al. Poster: P344 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Forsberg L Clinical Effectiveness of Cladribine Tablets for Patients Below or Above 50 Years of Age at Treatment Start in the Swedish Post-market Surveillance Study "Immunomodulation and Multiple Sclerosis Epidemiology 10" (IMSE 10) Larsson V, Forsberg L, Hillert J, et al. Poster: P861 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Larsson V CLADCOMS - CLADribine Tablets Long-term Control of MS – a Post-Marketing Investigator Driven Study Larsson V, Forsberg L, Nilsson P, et al. Poster: P865 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Larsson V Clinical Effectiveness of Cladribine Tablets for Patients with Few vs Many Treatments Prior CladT Initiation in the CLADCOMS Study -CLADribine Tablets Long-term Control Of MS – a Post-marketing Investigator Driven Study Larsson V, Forsberg L, Nilsson P, et al. Poster: P1804 Session: ePoster Date: September 24-26, 2025 Presenter: Larsson V Recurrent Effects on the Clonal Composition of Peripheral B Cells in MS Patients During the Second Year of Cladribine Treatment Tieck MP, Vasilenko N, Stadelmaier J, et al. Poster: P813 Session: Poster Session 2 Date: September 25, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Tieck MP Preliminary Data of Paramagnetic Rim Lesion Dynamic at 7 Tesla Magnetic Resonance Imaging in Cladribine Tablets-Treated People with Multiple Sclerosis Dal-Bianco A, Hametner S, Grabner G, et al. Poster: P216 Session: Poster Session 1 Date: September 24, 2025 Time: 07:30-09:30 am PDT/10:30 am-12:30 pm EDT Presenter: Dal-Bianco A Baseline and Early Safety Data Following Full Recruitment of ChariotMS, the First DMT trial for People with Advanced MS (EDSS 6.5-8.5) Schmierer K, Mattoscio M, De Angelis F, et al. Poster: P1633 Session: ePoster Date: September 24-26, 2025 Presenter: Schmierer K Breaking Inflammatory Cycles: Cladribine Targets Pathogenic B Cell Subsets in Multiple Sclerosis Pirronello M, Picozza M, Corbisiero S, et al. Poster: P1374 Session: ePoster Date: September 24-26, 2025 Presenter: Battistini L Circulating MicroRNAs as Potential Biomarkers for Treatment Response in Cladribine-Treated Multiple Sclerosis Patients Vigiser I, Zeevi Y, Piura Y, Kolb H, Golan M, Karni A, Regev K Poster: P762 Session: ePoster Date: September 24-26, 2025 Presenter: Vigiser I Integrin β1 Demarks Circulating Precursors of Brain-residing Antibody-secreting Cells in People with MS Kuiper K, Bogers L, Rip J, et al. Oral presentation: O123 Session: Scientific Session 14: Antibody-mediated pathology Date: September 26, 2025 Time: 12:26-12:33 am PDT/03:26-03:33 am EDT Presenter: Smolders J Early Lymphocyte Reduction as a Potential Marker of Cladribine Efficacy Celius E, et al. Poster: P2028 Session: ePoster Date: September 24-26, 2025 Presenter: Celius E 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. More than 130,000 patients have been treated with MAVENCLAD since its launch in 2019. MAVENCLAD has been approved in over 80 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit www.MAVENCLAD.com for more information. IMPORTANT SAFETY INFORMATION WARNING: MALIGNANCIES and RISK OF TERATOGENICITY 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 infected 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 on a MAVENCLAD treatment day 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. Concomitant use of MAVENCLAD with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects. Monitor lymphocyte counts before, during, and after treatment. Infections: Serious, including life-threatening or fatal, infections have occurred. MAVENCLAD reduces the body's immune defense, and an increased risk of infections has been observed in patients receiving MAVENCLAD. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% of patients treated with placebo in clinical studies; serious or severe infections occurred in 2.4% of MAVENCLAD- treated patients and 2.0% of placebo-treated patients. The most frequent serious infections included herpes zoster and pyelonephritis. Fungal infections were observed, including cases of coccidioidomycosis. Single fatal cases of tuberculosis and fulminant hepatitis B were reported in the clinical program. Hematologic Toxicity: In addition to lymphopenia, decreases in other blood cells and hematological parameters have been reported with MAVENCLAD in clinical studies. Obtain complete blood count (CBC) with differential including lymphocyte count before and during treatment, periodically thereafter, and when clinically indicated. 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. In patients who require blood transfusion, irradiation of cellular blood components is recommended. 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 MAVENCLAD if clinically significant liver injury is suspected. Hypersensitivity: 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. Instruct patients to seek medical advice if they experience symptoms of cardiac failure (e.g., shortness of breath, rapid or irregular heartbeat, swelling). Adverse Reactions: The most common adverse reactions (incidence of >20%) are upper respiratory tract infection, headache, and lymphopenia. Drug Interactions: Concomitant use of 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. Monitor for additive effects on the hematological provide with use of hemotoxic drugs. Avoid concomitant use of 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 >65 years, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended. To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono, Inc. at 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING, 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 2.9 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 in Neurology and Immunology EMD Serono has a long-standing legacy in neurology and immunology, with significant R&D and commercial experience in multiple sclerosis (MS). The company’s current MS portfolio includes two products for the treatment of relapsing MS – Rebif® (interferon beta-1a) and MAVENCLAD® (cladribine) tablets. EMD Serono aims to improve the lives of patients by addressing areas of unmet medical needs. In addition to EMD Serono’s commitment to MS, the company also has a pipeline focusing on discovering new therapies that have potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE) and generalized myasthenia gravis (gMG). 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 1,050 employees around the country with commercial, clinical and research operations in Massachusetts. www.emdserono.com. About Merck KGaA, Darmstadt, Germany Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across life science, healthcare and electronics. More than 62,000 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 providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2024, Merck KGaA, Darmstadt, Germany, generated sales of € 21.2 billion in 65 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.