EMD Serono Completes Enrollment of Evobrutinib Phase III Clinical Trials Ahead of ECTRIMS 2021
October 4, 2021- Investigational evobrutinib is the first Bruton’s tyrosine kinase (BTK) inhibitor to complete Phase III clinical trial enrollment in relapsing multiple sclerosis (RMS)
- Data from oral presentations at ECTRIMS show evobrutinib has a positive impact on important biomarkers of disease progression
- New independent data being presented found that patients treated with MAVENCLAD® (cladribine) tablets had increased antibody IgG titer levels similar to that of the general population after a complete course of an mRNA COVID-19 vaccine
ROCKLAND, Mass.–(BUSINESS WIRE)–EMD Serono, the Healthcare business sector of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced enrollment has been completed in the Phase III EVOLUTION RMS clinical trial program, which is evaluating the efficacy and safety of investigational Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib in patients with relapsing multiple sclerosis (RMS). This milestone comes just ahead of the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place virtually from October 13-15, 2021, where 39 abstracts from the Company’s multiple sclerosis (MS) portfolio will be presented. Data will include two oral presentations and a late-breaking ePoster on evobrutinib as well as late-breaking ePosters on MAVENCLAD® (cladribine) tablets including new interim data on patient-reported improvements in quality of life (QoL) and new independent data on MAVENCLAD patients who have received a complete course of an mRNA COVID-19 vaccine.
“The breadth of our data at ECTRIMS, paired with the rapid enrollment in our evobrutinib Phase III EVOLUTION RMS clinical trial program, further exemplifies a commitment to continue breaking boundaries in the science of MS,” said Danny Bar-Zohar, Global Head of Development for the Healthcare business of Merck KGaA, Darmstadt, Germany. “By generating new data on MAVENCLAD to demonstrate the positive real-life impact it can have for people with RMS, and also on progressing evobrutinib with its dual mode of action targeting both B-cells and innate immune cells in the central nervous system and periphery, we are hoping to address the needs of people with RMS now and in the future.”
Key MAVENCLAD® (cladribine) tablets data include:
- Updated post-approval safety data of MAVENCLAD demonstrating consistency of real-world experience with the profile reported in the Phase III and ongoing Phase IV trials, and providing evidence that patients receiving MAVENCLAD do not appear at increased risk of severe COVID-19 outcomes
- In an independent open label study, patients treated with MAVENCLAD were found to increase antibody immunoglobulin G (IgG) titer levels similar to healthy controls after a complete course of an mRNA COVID-19 vaccine. In the U.S., the MAVENCLAD label states that all immunizations should be administered according to immunization guidelines prior to starting MAVENCLAD
- A new interim analysis from the Phase IV CLARIFY-MS study demonstrating that patients living with RMS reported an improvement in physical and mental health at one year of MAVENCLAD treatment
- Real-world MAVENCLAD data from the MSBase Registry demonstrating adherence to MAVENCLAD and an annualized relapse rate similar to clinical trial data
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Late-breaking data including:
- Long-term Efficacy for Patients Receiving Cladribine Tablets in CLARITY/CLARITY Extension: Primary Results from 9–15 Years of Follow-up in the CLASSIC-MS Study
- Cladribine tablets after treatment with natalizumab (CLADRINA) trial – Interim analyses
Key evobrutinib data include:
- Data from a post-hoc analysis in the Phase II trial with evobrutinib demonstrated a reduction in volume of slowly expanding lesions (SELs), an in-vivo magnetic resonance imaging (MRI) correlate of chronic active inflammation and axonal loss within the central nervous system (CNS), which may be predictive of subsequent clinical disease progression in MS
- Results from the same trial showed that increased levels of blood neurofilament light chain (NfL), a marker of neuronal damage, at baseline were predictive of increased relapse and MRI lesion activity in the study and evobrutinib significantly reduced MRI and relapse outcomes
- Extensive safety profile characterization of evobrutinib in over 1000 patients from Phase II clinical trials in MS, rheumatoid arthritis and systemic lupus erythematosus demonstrating that overall evobrutinib treatment (all doses) was generally well tolerated across indications and elevations in liver enzymes were asymptomatic and reversible
Additional Company activities at ECTRIMS 2021:
- Satellite symposium: “Supporting patient needs in MS every step of the way” co-chaired by Prof. Gavin Giovannoni, Chair of Neurology, Barts and The London School of Medicine and Dentistry and Prof. Barbara Kornek, Department of Neurology at the University of Vienna (October 13, 2021, 9:00-10:00 EDT)
- Medical education symposium “MS innovation in practice: the continuing search for novel therapeutic targets” co-chaired by Prof. Patrick Vermersch, Vice President for research in biology and health at the University of Lille, and Dr. Xavier Montalban, Chairman & Director Neurology-Neuroimmunology Department & Neurorehabilitation Unit, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital, Barcelona, Spain (October 13, 2021, 11:45-12:45 EDT).
To keep up-to-date with our activities at ECTRIMS, along with future data and information, follow us on Twitter @EMDSerono and LinkedIn: EMD Serono, Inc. #ECTRIMS2021 #MSInsideOut
Below is the full list of EMD Serono-related abstracts accepted for presentation at ECTRIMS 2021:
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Oral Presentations: |
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Abstract Name |
Authors |
Presentation ID |
Presentation Details |
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Effects of evobrutinib, a Bruton’s tyrosine kinase inhibitor, on slowly expanding lesions: an emerging imaging marker of chronic tissue loss in multiple sclerosis |
D.L. Arnold, C. Elliott, X. Montalban, E. Martin, Y. Hyvert, D. Tomic |
115 |
Session: Free Communications 2 – Treatment trials – Immunomodulation |
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Evobrutinib significantly reduces relapses and magnetic resonance imaging outcomes in patients with multiple sclerosis: association with baseline neurofilament light chain levels |
J. Kuhle, L. Kappos, X. Montalban, Y. Li, K. Thangavelu, Y. Hyvert, D. Tomic |
116 |
Session: Free Communications 2 – Treatment trials – Immunomodulation |
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Single cell analysis of cerebrospinal fluid leukocytes in treated multiple sclerosis patients |
M. Heming, I. Lu, N. Schwab, D. Schafflick, C.C. Gross, H. Wiendl, G.M. zu Horste |
134 |
Session: Free Communication 3: Pathology |
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Activated Tfh1 cells infiltrate the cerebrospinal fluid in early multiple sclerosis |
J.Morille, M. Mandon, S.Rodriguez, A.Garcia, S.Wiertlewski, L.Berthelot, K.Tarte, C.Delaloy, P.Amé, D-A.Laplaud, L.Michel |
025 |
Session: Scientific Session 2: Blood-Brain Barrier |
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MAVENCLAD® (cladribine) tablets ePoster Presentations: |
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Long-term Efficacy for Patients Receiving Cladribine Tablets in CLARITY/CLARITY Extension: Primary Results from 9–15 Years of Follow-up in the CLASSIC-MS Study |
G. Giovannoni, T. Leist, A. Aydemir, E. Verdun Di Cantogno, on behalf of the CLASSIC-MS Steering Committee |
P975 |
Date: October 13, 2021 |
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Cladribine Tablets after treatment with natalizumab (CLADRINA) trial – Interim analyses |
P. Sguigna, A. Okai, J. Kaplan, K. Blackburn, L. Tardo, B. Hayward, U. Boschert, L. Lebson, N. Manouchehri, R. Hussain, O. Stuve |
P987 |
Date: October 13, 2021 |
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Improvements in QoL at 1 Year in Patients Treated With Cladribine Tablets for Highly Active Relapsing MS: An Interim Analysis of CLARIFY-MS |
A. Solari, X. Montalban, J. Lechner-Scott, F. Piehl, B. Brochet, D. Langdon, R. Hupperts, K. Selmaj, E.K. Havrdova, F. Patti, Brieva L, Maida EM, N. Alexandri, P. Kamudoni, A. Nolting, B. Keller |
P238 |
Date: October 13, 2021 |
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Post-Approval Safety of Cladribine Tablets With Particular Reference to COVID-19 Outcomes: An Update |
G. Giovannoni, J. Berger, T. Leist, D. Jack, A. Galazka, A. Nolting, D. Damian |
P766 |
Date: October 13, 2021 |
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High Adherence to Treatment With Cladribine Tablets for Multiple Sclerosis: Value-Added Benefit of a Nurse/Pharmacy-led Patient Support Programme During the COVID-19 Pandemic |
J. Oh, M.S. Freedman, K. Vernon, M. Ayer, C. Lemieux, K. Morgan, T. Quinn, T. Vella, A. Allignol, M. Stein, E. Verdun di Cantogno, M. Sabidó |
P741 |
Date: October 13, 2021 |
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Incidence of Infections and Severe Lymphopenia in Patients Newly Initiating Cladribine Tablets or Fingolimod for Treatment of Multiple Sclerosis: CLARION Study |
J. Hillert, H. Butzkueven, M. Soilu-Hänninen, T. Ziemssen, J. Kuhle, J.R. Berger, A. Aydemir, J. Sõnajalg, I. Bezemer, M. Sabidó |
P767 |
Date: October 13, 2021 |
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Disease-Modifying Treatment Patterns of Patients With Multiple Sclerosis and Newly Treated With Cladribine Tablets or Fingolimod: An Interim Analysis of the CLARION Study |
H. Butzkueven, J. Hillert, J. Sõnajalg, M. Soilu-Hänninen, A. Aydemir, T. Ziemssen, J. Kuhle, M. Magyari, S. Wergeland, I. Bezemer, M. Sabidó
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P742 |
Date: October 13, 2021 |
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Risk of Cancer with Disease-Modifying Drugs in Multiple Sclerosis: A New-User Cohort Design in the French Nationwide Claims Database |
P. Bosco-Lévy, M. Sabidó, E. Guiard, P. Diez, C. Foch, C. Favary, J. Jové, E. Boutmy, P. Blin |
P756 |
Date: October 13, 2021 |
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A Multi-Country Cohort Database Study to Assess Pregnancy and Infant Outcomes in Women Exposed to Cladribine Tablets: CLEAR Study |
K. Hellwig, M. Magyari, T. McDonald, K. Gembert, S. Wergeland, M.k. Leinonen, A. Aydemir, M. Sabidó, A. Kawai, A. Arana
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P185 |
Date: October 13, 2021 |
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MASTER-2 trial: Cladribine tablets in patients with relapsing-remitting multiple sclerosis and active secondary multiple sclerosis after suboptimal response to prior infusion/oral disease-modifying therapy (interim baseline results) |
E.J. Fox, A.D. Bass, J. Aldridge, L.A. Lebson, D. Robertson |
P851 |
Date: October 13, 2021 |
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Evaluation of therapy satisfaction with cladribine tablets in RMS patients – Final results of the non-interventional study CLEVER |
C. Grothe, L. Cepek, G. Reifschneider, T. Ziemssen, J. Richter, T. Wagner |
P859 |
Date: October 13, 2021 |
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Finnish cladribine tablets registry study 2 year data |
S. Atula, E. Jarvinen, H. Kuusisto, I. Rauma, M. Ryytty, J. Sipilä, M. Soilu-Hänninen, M. Viitala |
P691 |
Date: October 13, 2021 |
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Outcomes after late Cladribine re-dosing in the Australian MSBase cohort |
H. Butzkueven, T. Spelman, S. Hodgkinson, A. Van der Walt, K. Buzzard, O. Skibina, T. Kalincik, J. Lechner-Scott, R. Macdonell, E. Verdun di Cantogno |
P865 |
Date: October 13, 2021 |
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Real-world experience with cladribine in the MSBase Registry |
H. Butzkueven, T. Spelman, MSBase Investigators (TBC), E. Verdun di Cantogno |
P825 |
Date: October 13, 2021 |
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Molecular biomarker signature associated with cladribine treatment |
N. Fissolo, L. Calvo-Barreiro, H. Eixarch, U. Boschert, C. Espejo, X. Montalban, M. Comabella |
P584 |
Date: October 13, 2021 |
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Effect of cladribine on differentiation of human neural precursor cells |
H. Eixarch, L. Calvo-Barreiro, N. Fissolo, U. Boschert, M. Comabella, X. Montalban, C. Espejo |
P899 |
Date: October 13, 2021 |
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Economic Analysis for Introduction of Cladribine Tablets as a Treatment for Relapsing-Remitting and High Disease Activity Multiple Sclerosis in Kuwait |
R. Alroughani, M.A. Al-Melh, S. Farouk, A. Abokoura, E. Alsultan, A Boshra, R. Alcharif, R. Ojeil, S. Basu, A. Verma |
P280 |
Date: October 13, 2021 |
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Effect of cladribine on COVID-19 serology responses following 2 doses of the BNT162b2 mRNA vaccine in patients with multiple sclerosis |
A. Vaknin-Dembinsky |
P780 |
Date: October 13, 2021 |
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Effect of cladribine tablets in highly active MS monitored by global and regional brain atrophy status |
A. Raji, G. Winkler |
P709 |
Date: October 13, 2021 |
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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) |
V. Rosengren, E. Ekström, L. Forsberg, S. Kågström, J. Hillert, P. Nilsson, C. Dahle, A. Svenningsson, J. Lycke, A-M. Landtblom, J. Burman, C. Martin, P. Sundström, M. Gunnarsson, F. Piehl, T. Olsson |
P743 |
Date: October 13, 2021 |
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Real-world patient profile of cladribine tablets in multiple sclerosis patients from Argentina |
Rojas JI, Alonso R, Luetic G, Pappolla A, Miguez J, Patrucco L, Cohen L, Garcea O, Casas M, Silva B, Deri N, Liwacki S, Silva E, Piedrabuena R et al. |
P853 |
Date: October 13, 2021 |
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Seroconversion following vaccination against SARS-CoV-2 in people with MS: impact of disease modifying therapy |
N. Vickaryous, A.N. Asardag, J. Bestwick, S.N. Shah, K. George, K. Schmierer, G. Giovannoni, D. Baker, A. Kang, R. Dobson |
P950 |
Date: October 13, 2021 |
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Rebif® (interferon beta-1a) subcutaneous injection ePoster Presentations: |
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Development and Interrelation of Whole-Brain Atrophy and Lesion Volume During 5 Years’ Treatment With Subcutaneous Interferon Beta-1a in Patients With a First Clinical Demyelinating Event in the REFLEX/ION Study |
R.M. Mattiesing, G. Gentile, I. Brouwer, D. Jack, A. Seitzinger, F. Barkhof, N. De Stefano, B.M.J. Uitdehaag, J.W.R. Twisk, M. Battaglini, H. Vrenken |
P430 |
Date: October 13, 2021 |
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Development and Interrelation of Spatiotemporal Patterns of Brain Atrophy and Lesions During 5 Years’ Treatment With Subcutaneous Interferon Beta-1a in Patients With a First Clinical Demyelinating Event in the REFLEX/ION Study |
G. Gentile, R.M. Mattiesing, I. Brouwer, D. Jack, A. Seitzinger, F. Barkhof, N. De Stefano, B.M.J. Uitdehaag, H. Vrenken, M. Battaglini |
P458 |
Date: October 13, 2021 |
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Exploratory Analysis of Serum GDF-15 Levels in Patients Receiving Subcutaneous Interferon Beta-1a in the REFLEX Trial |
M. Coray, A. Seitzinger, S. Roy, M.S. Freedman, F. Barkhof, G. Comi, N. De Stefano, L. Kappos, J. Kuhle, M. Mehling |
P674 |
Date: October 13, 2021 |
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INFORM – Interferon-Beta Exposure in the 2nd and 3rd Trimester of Pregnancy – a Register-Based Drug Utilisation Study in Finland and Sweden |
M. Sabidó, K. Suzart-Woischnik, N. Grimes, L.M. Prach, L. Zhao, K.M. Hakkarainen |
P794 |
Date: October 13, 2021 |
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Evobrutinib ePoster Presentations: |
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Safety profile characterization of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus |
X. Montalban, D. Wallace, M.C. Genovese, D. Tomic, D. Parsons-Rich, C. Le Bolay, A. Kao, H. Guehring |
P727 |
Date: October 13, 2021 |
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The role of human and mouse BTK in myeloid cells |
C. Bassani, M. Molinari, V. Martinelli, R. Grenningloh, U. Boschert, G. Comi, G. Martino, L. Muzio, C. Farina |
P656 |
Date: October 13, 2021 |
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Targeting BTK in chronic CNS autoimmunity inhibits activation of microglia |
A. Geldaris, S. Torke, R. Grenningloh, U. Boschert, W. Brück, M.S. Weber |
P971 |
Date: October 13, 2021 |
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Non-Product Specific ePoster Presentations: |
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DISCOntinuation of disease-modifying therapies in MS (DISCOMS) Extension – Study Design and Baseline Demographics |
E. Engebretson, G. Cutter, R. Fox, I. Kister, A. Miller, C. Morgan, R. Seale, J.R. Corboy |
P751 |
Date: October 13, 2021 |
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Genome-wide mapping of patient’s autoantibody targets to understand and predict Multiple Sclerosis pathogenesis and patient responses to Interferon β-1a therapy |
E.B. DiCillo, E. Kountikov, M. Zhu, W. Zhang, B. Hayward, D.E. Harlow, S. Lanker, J.L. Bennet, T.F. Tedder |
P361 |
Date: October 13, 2021 |
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Towards a new resource for the MS brain: a cross-brain bank proteomic atlas of non-lesional neocortex |
P. Bouman, D. Pitt, D. Reich, J. Schneider, D. Bennett, R. Nagra, R. Reynolds, J. Geurts, J. Corboy, P. De Jager |
P317 |
Date: October 13, 2021 |
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Multiplexed imaging of the multiple sclerosis meninges using mass cytometry |
V. Ramaglia, M. Zuo, N. Fransen, S. Zandee, A. Prat, I. Huitinga, A. Bar-Or, J.L. Gommerman |
P319 |
Date: October 13, 2021 |
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Interprofessional collaboration and patient-provider communication challenges in MS care: A mixed-methods needs assessment |
S. Péloquin, K. Schmierer, J. Oh, T. Leist, S. Murray, P. Lazur |
P903 |
Date: October 13, 2021 |
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Neuropsychological measures associated with disease severity in pediatric onset multiple sclerosis |
N. Gur, E. Ganelin Cohen, T. Pilowsky Peleg |
P990 |
Date: October 13, 2021 |
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 www.MAVENCLAD.com 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.
Contacts
Alice McGrail
[email protected]
1-781-681-2886