Investigational evobrutinib is the first Bruton’s tyrosine kinase (BTK) inhibitor to complete Phase III clinical trial enrolment 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 also 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
Not intended for UK and U.S. based media
DARMSTADT, Germany -- (BUSINESS WIRE) --
Merck, a leading science and technology company, today announced enrolment has been completed in the Phase III EVOLUTION RMS clinical trial programme, 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 13-15 October 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 enrolment in our evobrutinib Phase III EVOLUTION RMS clinical trial programme, 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. “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 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
- 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 annualised 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
- Safety profile characterisation 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 (13 October 2021, 15:00–16:00 CEST)
- 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 (13 October 2021, 17:45-18:45 CEST). Medical and healthcare journalists interested in attending can register at merckneurology.com/newsroom
To keep up-to-date with our activities at ECTRIMS, along with future data and information, visit merckneurology.com/newsroom or follow us on Twitter @MerckHealthcare and LinkedIn: Healthcare Business of Merck #ECTRIMS2021 #MSInsideOut
Below is the full list of Merck-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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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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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 |
P742 |
Date: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 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: 13 October 2021 |
About MAVENCLAD®
MAVENCLAD® is a short-course oral therapy that selectively and periodically targets lymphocytes thought to be integral to the pathological process of relapsing MS (RMS). In August 2017, the European Commission (EC) granted marketing authorization for MAVENCLAD® for the treatment of relapsing forms of multiple sclerosis (RMS) in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. MAVENCLAD® has since then been approved in over 80 countries, including Canada, Australia and the U.S. Refer to the respective prescribing information for further details.
The clinical development programme for cladribine tablets includes:
- The CLARITY (Cladribine Tablets Treating MS Orally) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients with RRMS.
- The CLARITY extension study: a Phase III placebo-controlled study following on from the CLARITY study, which evaluated the safety and exploratory efficacy of cladribine tablets over two additional years beyond the two-year CLARITY study, according to the treatment assignment scheme for years 3 and 4.
- The ORACLE MS (Oral Cladribine in Early MS) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS).
- The ONWARD (Oral Cladribine Added ON to Interferon beta-1a in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled study designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy.
- PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis) study: a long-term observational follow-up safety registry of MS patients who participated in cladribine tablets clinical studies.
In the two-year CLARITY study, the most commonly reported adverse event (AE) in patients treated with cladribine tablets was lymphopenia (26.7% with cladribine tablets and 1.8% for placebo). The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% respectively rated mild-to-moderate by investigators. Adverse Events reported in other clinical studies were similar.
About Rebif®
Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS) and is similar to the interferon beta protein produced by the human body. The efficacy of Rebif® in chronic progressive MS has not been established. Interferon ß is thought to help reduce inflammation. The exact mechanism is unknown.
Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 90 countries worldwide. Rebif® has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area*.
Rebif® can be administered with the RebiSmart® electronic auto-injection device (not approved in the US), or with the RebiDose® single-use disposable pen, or the manual multidose injection pen RebiSlide™. Rebif® can also be administered with the autoinjector Rebiject II® or by manual injection using ready-to-use pre-filled syringes. These injection devices are not approved in all countries.
In January 2012, the European commission approved the extension of the indication of Rebif® in early multiple sclerosis. The extension of the indication of Rebif® has not been submitted in the United States.
Rebif® should be used with caution in patients with a history of depression, liver disease, thyroid abnormalities and seizures. Most commonly reported side effects are flu-like symptoms, injection site disorders, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors.
*The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.
Rebif® (interferon beta-1a) is approved in the United States for relapsing forms of MS.
About Evobrutinib
Evobrutinib (M2951) is in clinical development to investigate its potential as a treatment for multiple sclerosis (MS). It is an oral, highly selective inhibitor of Bruton’s tyrosine kinase (BTK) which is important in the development and functioning of various immune cells including B lymphocytes and macrophages. Evobrutinib is designed to inhibit primary B cell responses such as proliferation and antibody and cytokine release, without directly affecting T cells. Evobrutinib is currently under clinical investigation and not approved for any use anywhere in the world.
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.
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 the potential in other neuroinflammatory and immune-mediated diseases, including systemic lupus erythematosus (SLE).
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About Merck
Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 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 2020, Merck generated sales of € 17.5 billion in 66 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 EMD Serono in healthcare, MilliporeSigma in life science and EMD Electronics.
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CONTACT:
Tone Brauti Fritzen
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