Merck will present 39 abstracts at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
• Company’s scientific leadership will be highlighted in 39 abstracts presented across its multiple sclerosis (MS) portfolio
• Data on investigational BTK inhibitor evobrutinib demonstrate long-term disease stability in people living with relapsing MS (RMS)
• Phase IV study highlights improvement in measures of Quality of Life in people living with RMS after two years of treatment with MAVENCLAD® (cladribine tablets)
Merck, a leading science and technology company, today announced it will present 39 abstracts at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held October 26-28, 2022 in Amsterdam, the Netherlands.
The breadth of data highlights the Company’s scientific leadership in multiple sclerosis (MS) and includes a presentation on a clinical trial with long-term data on Expanded Disability Status Scale (EDSS) scores in people with relapsing MS (RMS) treated with evobrutinib, an investigational agent, as well as new data demonstrating MAVENCLAD® (cladribine tablets) improved Quality of Life (QoL) in people with highly active RMS over two years. Additionally, a two-year follow-up study showed the onset of action on the reduction of MRI lesions with MAVENCLAD being maintained from Month 2 through two years.
“Multiple sclerosis has a profound impact on quality of life and improving this through therapy is often the most important outcome for people living with MS,” said Gavin Giovannoni, Professor of Neurology, Queen Mary University of London. “The data presented at ECTRIMS further substantiate the therapeutic benefit of MAVENCLAD by improving Quality of Life measures over two years, combined with new evidence that the early effect on MRI lesions is maintained over that period.”
In the final analysis of the open-label, single-arm, multicenter, Phase IV CLARIFY-MS study, statistically significant (p≤0.0001) improvements from baseline were observed for Multiple Sclerosis Quality of Life-54 (MSQoL-54) physical and mental health composite scores (mean changes of 4.86 and 4.80, respectively; p<0.0001). Changes in MSQoL-54 composite scores were consistent across treatment naïve and prior disease-modifying treatment (DMT) subgroups. Annualized relapse rate was 0.13 in all patients (0.08 in patients who had not received DMT prior to receiving MAVENCLAD) and median EDSS was unchanged over two years. No new safety concerns emerged.
Also to be presented are new MRI outcomes data from the Phase IV MAGNIFY-MS study, which demonstrated an onset of action from Month 2 with sustained reduction in MRI lesion counts maintained out to two years in people with highly active RMS treated with MAVENCLAD. The proportion of lesion-free patients increased from 47% at baseline to 86.2% at the end of the study (Month 18–24). In the study, MRI lesions at baseline were compared over multiple time periods, from initial screening to Month 24. Over the two years, the benefit:risk profile of MAVENCLAD remained unchanged and in line with observations made during the clinical trial program.
Additionally, updated post-approval safety data will be presented based on an analysis of 56,300 patients who received MAVENCLAD post-approval, representing 95,664 patient-years of experience, as of July 2022. The study found the safety profile of MAVENCLAD is consistent with findings from the clinical development program and the CLARIFY-MS and MAGNIFY-MS studies.
“The breadth of our data at ECTRIMS exemplifies our commitment to pushing forward scientific innovation with the development of evobrutinib, while generating new, meaningful data to demonstrate the safety profile and effectiveness of MAVENCLAD,” said Jan Klatt, Senior Vice President, Head of Development Unit Neurology & Immunology at Merck. “Our goal is to ensure people living with MS, and those who treat them, have the information they need to manage their MS today and in the future.”
Beyond the MAVENCLAD and evobrutinib data presented, Merck will have several Company events, along with additional data from its MS portfolio at ECTRIMS 2022.
Company activities at ECTRIMS 2022:
• “Connecting the dots: immune cells and CNS inflammation” co-chaired by Professor Gavin Giovannoni, MBBCh, PhD, FCP (Neurol., SA), FRCP, FRCPath, Blizard Institute, Barts and the London School of Medicine and Dentistry, UK, and Celia Oreja-Guevara, MD, PhD, Hospital Clínico San Carlos, Madrid, Spain (October 26, 2022, 13:15-14:15 CEST)
• “New tools for new challenges in multiple sclerosis” chaired by Stephen Krieger, MD, Mount Sinai Hospital, New York, NY, USA (October 28, 2022, 14:15-15:15 CEST)
• Product Theater: Early Experience with MAVENCLAD by Ravi Dukkipati, MD, WellSpan Neurology, York, PA, USA
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
Below is the full list of Merck-related abstracts accepted for presentation at ECTRIMS 2022:
Abstract Name Authors ID Presentation Details
MAVENCLAD Poster Presentations
Improvements in Quality of Life Over 2 Years in Patients Treated With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: Final Analysis of CLARIFY-MS
Solari A, Montalban X, Lechner-Scott J, Piehl F, Brochet B, Langdon D, Hupperts R, Selmaj K, Havrdova EK, Patti F, Brieva L, Maida EM, Alexandri N, Smyk A, Nolting A, Keller B, on behalf of the CLARIFY Investigators P108
Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Jeannette Lechner-Scott
Early Onset of Action and Sustained Efficacy of MRI Outcomes during Cladribine Tablets Treatment in Highly Active Relapsing Multiple Sclerosis: Results of the 2-year MAGNIFY-MS Study
De Stefano N, Achiron A, Barkhof F, Chan A, Derfuss T, Hodgkinson S, Leocani L, Montalban X, Prat A, Schmierer K, Sellebjerg F, Vermersch P, Wiendl H, Keller B, Smyk A, Gardner L P717 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Nicola De Stefano
Updated Post-Approval Safety of Cladribine Tablets in the Treatment of Multiple Sclerosis, With Particular Reference to Liver Safety Giovannoni G, Leist T, Jack D, Galazka A, Nolting A
P341 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Gavin Giovannoni
High Adherence and Minimal Delays of Year 2 Treatment in People with Multiple Sclerosis Treated with Cladribine Tablets: Results from Multi-Country Patient Support Programmes Oh J, Ayer M, Alroughani R, Lemieux C, Morgan K, D’Eramo M, Vella T, Boshra A, de Souza S, Verdun di Cantogno E, Sabidó M P727 Session: 2
Date: October 27, 2022
Time: 17:00 CEST
Presenter: Jiwon Oh
Treatment Emergent Adverse Events Experienced Early and Transiently in the Treatment Course with Cladribine Tablets: Data from the CLEVER Real-World Study Ziemssen T, Posevitz-Fejfar, Wagner T, Übler S, Richter J, Müller B, Penner I-K P772 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Talf Ziemssen
Maven4: Phase IV Non-Interventional, Prospective, Spanish Multicenter Study to Evaluate Cladribine Tablets Long Term Effectiveness on Real-World Clinical Practice Saiz A, Aladro Benito Y, Costa-Frossard F, Sánchez Magro I, Rodríguez Antigüedad A
P774 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Albert Saiz
Cladribine Protects SH-SY5Y Neuron-Like Cells from Oxidative Stress Conditions In Vitro
Eixarch H, Calvo-Barreiro L, Fissolo N, Boschert U, Comabella M, Montalban X, Espejo C P784 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Herena Eixarch
Real-World Use of Cladribine Tablets (Completion Rates and Treatment Persistence) in Patients With Multiple Sclerosis in England: The CLARENCE Study Brownlee W, Amin A, Herbert A, Ashton L
P762 Session: 2
Date: October 27, 2022
Time: 17:00 CEST
Presenter: Wallace Brownlee
Decision-making Factors in Patient Choice to Initiate Treatment with Cladribine: A Preliminary Baseline Analysis From the STATURE Study Allan M, Grech L, Cartwright A, Harding J, Mardan J, O’Maley J, Savickas S, Sharma M, Murambiwa P, Stockle P, Bardsley B, Butler E P304 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Michelle Allan
Assessment of Treatment Satisfaction Across Oral DMTs for Multiple Sclerosis: a Preliminary Baseline Analysis from the STATURE Study. Grech L, Allan M, Cartwright A, Harding J, Mardan J, O’Maley T, Savickas S, Sharma M, Murambiwa P, Stockle P, Bardsley B, Butler E EP1086 Session: ePoster
Date: October 26-28, 2022
A Real-World Study of Four-Year Follow Up Study of Patients Treated with Oral Cladribine From 2018-2022 O’Neill DTD, Sharma M, Dong G, Hodgkinson SJ EP1132 Session: ePoster
Date: October 26-28, 2022
A Study of Activated and Naïve T Regs and B Cell Subsets For 30 Months After the Use of Cladribine Hodgkinson SJ, O’Neill DTD, Sharma M, Dong G, Verma ND, Al-atiyah R, Hall BM P704 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Suzanna Hodgkinson
CLADCOMS – CLADribine Tablets Long-Term Control of MS – a Post-Marketing Investigator Driven Study Fink K, Nilsson P, Alonso L, Sveningsson A, Gunnarsson M, Lange N, Ayad A, Vrethem M, Burman J, Lycke J, Piehl F EP1060 Session: ePoster
Date: October 26-28, 2022
Clinical Effectiveness and Safety of Cladribine Tablets for Patients Treated at least 12 Months in the Swedish Post-Market Surveillance Study “Immunomodulation and Multiple Sclerosis Epidemiology 10” (IMSE 10) Rosengren V, Ekström E, Forsberg L, Hillert J, Nilsson P, Dahle C, Svenningsson A, Lycke J, Landtblom A-M, Burman J, Martin C, Sundström, Gunnarsson M, Piehl F, Olsson T P728 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Linda Forsberg
SARS-CoV2 Exposure Rates and Serological Response of People Living With MS Longinetti E, Asplund K, Kockum I, Englund S, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, Hillert J, Langer-Gould A, Lycke J, Nilsson P, Salzer J, Svenningsson A, Mellergård J, Frisell T, Olsson T, Piehl F P558 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Elisa Longinetti
COVID-19 Humoral and T-cell Mediated Vaccination Responses in People with Multiple Sclerosis Vickaryous N, Rios F, Schalk L, Asardag AN, George K, Kang A, Baker D, Giovannoni G, Dobson R P781 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Nikki Vickaryous
Differences Between Clinical Trials and “Real-World” Use of Disease Modifying Therapies: Insights from the UK OPTIMISE:MS Pharmacovigilance Study Dobson R, Matthews P, Miller A, Pindoria J, Waddingham E P763 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Ruth Dobson
Cladribine Treatment Exerts Specific Effects on Memory B Cell Immunoglobulin Repertoires in Multiple Sclerosis Patients Ruschil C, Gabernet G, Kemmerer CL, Ziemann U, Nahnsen S, Kowarik MC EP1115 Session: ePoster
Date: October 26-28, 2022
Presenter: Christoph Ruschil
Cladribine Effects on T and B Cell Subsets and T Cell Reactivity in Multiple Sclerosis
Hansen RH, von Essen MR, Mahler MR, Cobanovic S, Binko TS, Sellebjerg F P697 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Rikke Holm Hansen
Safety and Efficacy of Cladribine Therapy Following a Treatment with Anti-CD20 Compounds in Relapsing Multiple Sclerosis Patients: A Pilot Study Sacco R, Disanto G, Pravatà E, Gobbi C, Zecca C
EP1068 Session: ePoster
Date: October 26-28, 2022
Evobrutinib Poster Presentations
Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, Maintains Lowered Serum Neurofilament Light Chain Levels Over 2.5 Years of Treatment, in Patients With Relapsing Multiple Sclerosis Kuhle J, Kappos L, Montalban X, Benkert P, Li Y, Thangavelu K, Hyvert Y, Tomic D
EP1021 Session: ePoster
Date: October 26-28, 2022
Presenter: Jens Kuhle
MRI and Clinical Outcomes of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, in Relapsing Multiple Sclerosis Over 2.5 Years of the Open-label Extension to a Phase II Trial Vermersch P, Arnold D, Wolinsky JS, Havrdova E, Kinkolykh A, Hyvert Y, Tomic D, Montalban X
P731 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Patrick Vermersch
Evobrutinib Exert a Therapeutic Action on EAE by Increasing the Peripheral and Central Classical Dendritic Cell Number and Maturation
Serrano-Regal MP, Calahorra L, Alonso-García I, Grenningloh R, Boschert U, Haselmayer P, Ortega MC, Machín-Díaz I, Camacho-Toledano C, García-Arocha J, Clemente D P307 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Mari Paz Serrano-Regal
Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor, Acts on Microglia: Implications in the Treatment of Progressive Mechanisms in Multiple Sclerosis Geladaris A, Torke S, Grenningloh R, Boschert U, Brück W, Weber MS
P693 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Anastasia Geladaris
B cells infiltrating the MS brain: from local maturation to targeting by evobrutinib
Bogers L, van Langelaar J, Rijvers L, Engelenburg HJ, Melief M-J, Wierenga-Wolf AF, Rip J, Blok KM, de Vries HE, Hendriks RW, Boschert U, Smolders J, van Luijn MM P147 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Laurens Bogers
Immune response following mRNA COVID-19 vaccination in patients with multiple sclerosis treated with the Bruton’s tyrosine kinase inhibitor evobrutinib Bar-Or A, Cross AH, Cunningham A, Hyvert Y, Seitzinger A, Drouin EE, Alexandri N, Tomic D, Montalban X P1188 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Amit Bar-Or
Rebif® (interferon beta-1a) Subcutaneous Injection Poster Presentations
Exploring the Relationship Between Serum GDF-15 and Disease Stability in Patients with a First Clinical Demyelinating Event Treated with Subcutaneous Interferon β-1a or Placebo in the REFLEX Study Coray M, Freedman MS, Barkhof F, Comi G, De Stefano N, Kappos L, Enz L, Seitzinger A, Jack D, Kuhle J, Mehling M EP1027 Session: ePoster
Date: October 26-28, 2022
Presenter: Mali Coray
Evolution of the RebiSmart® Autoinjector Device in Support of Adherence to Subcutaneous Interferon Beta-1a Therapy for Relapsing Multiple Sclerosis Arnaud L, Keiser M, Henninger E, Piras F, Seitzinger A, Jack D, Le Masne Q
EP1079 Session: ePoster
Date: October 26-28, 2022
Presenter: Dominic Jack
Validation of a Semi-Automated Method to Quantify Lesion Volume Changes in Multiple Sclerosis on 2D Proton Density- Weighted Images Using Subtraction Imaging Mattiesing RM, Stel S, Mangroe AS, Brouwer I, Versteeg A, van Schijndel RA, Uitdehaag BMJ, Barkhof F, Vrenken H P634 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Rozemarijn M Mattiesing
Expression of peripheral blood IFN-inducible genes predicts treatment outcome in patients with secondary progressive multiple sclerosis treated with IFN-beta-1a Gurevich M, Zilkha-Falb R, Menascu S, Magalashvili D, Dolev M, Sonis P, Mandel M, Achiron A
P353 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Michael Gurevich
Non-Product Specific Poster Presentations
DISCOntinuation of disease-modifying therapies in MS (DISCOMS) Extension – Study Design and Baseline Demographics to Date Engebretson E, Cutter G, Fox R, Kister I, Miller A, Morgan C, Seale R, Corboy JR
EP1089 Session: ePoster
Date: October 26-28, 2022
Expert Opinion on the Use of Contraception in People with Multiple Sclerosis
Hillert J, Bove R, Haddad L, Hellwig K, Houtchens M, Magyari M, Mercki G, Montgomery S, Nappi R, Stenager E, Thompson H, Tulek Z, Verdun di Cantogno E, Simoni M P080 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Jan Hillert
Single-Cell RNA Sequencing of Peripheral CD8+ T Cells of MS-Discordant Monozygotic Twins Reveals Disease-Associated Alterations In Immune Signaling Kavaka V, Mutschler L, Eglseer K, Flierl-Hecht A, Kümpfel T, Hohlfeld R, Kerschensteiner M, Gerdes L.A, Beltran E P159 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Vladyslav Kavaka
Caregiver Burden and Associated Factors Among Caregivers of
Persons with Multiple Sclerosis: Application of a Specific Instrument Vanotti S, Roman MS, Ferrandina F, Bauer J, Rosa R, Casas Parera I, Saladino ML, Caceres F
EP0864 Session: ePoster
Date: October 26-28, 2022
Presenter: Sandra Vannoti
Evolutionarily Conserved Signatures of Microglia in Health and Disease Salinas V, Manouchehri N, Hussain R, Stuve O
P131 Session: 1
Date: October 26, 2022
Time: 16:30- 18:30 CEST
Presenter: Victor Salinas
Peripheral Blood Immune Markers Associated With Immunosenescence in Multiple Sclerosis and Healthy Controls
Carpentier Solorio Y, Daigneault A, Tastet O, Clénet M-L, Farzam-kia N, Levert A, Da Cal S, Clément W, Jamann H, Laurent C, Mamane VH, Ouedraogo O, Moratalla AC, Balthazard R, Lahav B, Prat A, Girard J-M, Duquette P, Rousseau M-C, Arbour N, Larochelle C P545 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Catherine Larochelle
Chemerin Correlates with MS Progression Parameters and Affects Intracellular Metabolism in Human Microglia and Macrophages
Loonstra FC, van der Pol SM, Falize KF, van Heertum T, de Ruiter LR, Schoonheim MM, Killestein J, Uitdehaag BMJ, Kooij G, de Vries HE, Rijnsburger M P551 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Presenter: Merel Rijnsburger
Amyloid and some tau Proteinopathy are Observed in a Subset of Individuals with Multiple Sclerosis Taga M, Duquesne L, Lee A, Sigalov A, Peralta Cruz F, De Jager P P1204 Session: 2
Date: October 27, 2022
Time: 17:00- 19:00 CEST
Non-Product Specific Oral Presentations
Biological Roles of Myeloid Cell Subsets During CNS Inflammation Manouchehri N, Victor, Hussain RZ, Stuve O O124 Session: Young Scientific Investigators’ Session 3: Long-term outcomes and safety
Date: October 27, 2022
Time: 15:00- 16:00 CEST
Presenter: Navid Manouchehri
About Evobrutinib
Evobrutinib is an oral, highly selective CNS-penetrant inhibitor of Bruton’s tyrosine kinase (BTK) in clinical development as a potential treatment for relapsing multiple sclerosis (RMS). It is the first BTK inhibitor to demonstrate clinical efficacy in the largest Phase II study with follow-up beyond three years as well as demonstrate an impact on early biomarkers of ongoing central inflammation that correlate with disease progression. Evobrutinib is designed to modulate B cell responses such as proliferation and antibody and cytokine release, as well as modulate macrophage/microglia activation. It significantly reduced SEL volume and levels of blood NfL, markers of ongoing central inflammation and neurodegeneration that predict long-term disability. Evobrutinib was optimized for efficacy through the most comprehensive BTK inhibitor dose-finding study in RMS which demonstrated 75mg twice-daily dosing achieves maximal efficacy across endpoints by sustaining BTK inhibition throughout the dosing interval (>95% BTK occupancy maintained in 98% of patients before next dose). It is currently under clinical investigation and is not approved for any use anywhere in the world.
About MAVENCLAD®
MAVENCLAD, approved by the U.S. Food and Drug Administration (FDA) on March 29, 2019, is the first and only short-course oral therapy for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS). Patients should follow healthcare provider instructions including cancer screening, contraception and blood tests. The approved dose of MAVENCLAD is 3.5 mg per kg body weight over two years, administered as one treatment course of 1.75 mg per kg per year, each consisting of two treatment weeks. The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes. MAVENCLAD causes a dose-dependent reduction in lymphocyte counts followed by recovery.
Because cladribine is cytotoxic, special handling and disposal instructions should be followed.
MAVENCLAD has been approved in over 80 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit www.MAVENCLAD.com for more information.
About Rebif®
Rebif (interferon beta-1a) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It is used to decrease the frequency of relapses and delay the occurrence of some of the physical disability that is common in people with MS.
Geoffrey Vokes photo Merck KGaA