DARMSTADT, Germany--(BUSINESS WIRE)--Merck, a leading science and technology company, today announced that it will present data on its approved and investigational multiple sclerosis (MS) treatments at the 35th Congress of the European Committee for Treatment and Research In Multiple Sclerosis (ECTRIMS). During ECTRIMS, taking place from 11–13 September 2019, in Stockholm, Sweden, Merck will present 39 abstracts, including new long-term safety and efficacy data on MAVENCLAD® (cladribine tablets) and new safety data on pregnancy outcomes for interferon beta (IFN β) therapies, including Rebif® (interferon beta-1a). Data will also be presented further elucidating the proposed mechanism of action for investigational therapy evobrutinib, the first oral, highly selective Bruton’s Tyrosine Kinase (BTK) inhibitor to demonstrate clinical proof of concept in relapsing multiple sclerosis (RMS).
“The new data we will be sharing at ECTRIMS touch on several important topics for the scientific community, including long-term safety and efficacy data for MAVENCLAD, data on the use of interferon beta therapies, including Rebif in pregnancy, and data further elucidating evobrutinib’s unique proposed mechanism of action and its potential as a novel therapeutic approach in MS,” said Luciano Rossetti, Head of Global R&D for the Biopharma business of Merck. “These data reinforce the important role of our currently-available treatments and offer further insights on our investigational treatment, as we continue our unwavering commitment to address the needs of the MS community.”
Key MAVENCLAD data include:
- A post hoc analysis evaluating five-year disease stability in patients enrolled in the CLARITY and CLARITY EXTENSION trials, which showed sustained efficacy of MAVENCLAD on disability progression at five years after starting treatment
- Results from an exploratory analysis of real-world data from an Italian MS registry assessing time-to-treatment change after MAVENCLAD, which demonstrated sustained efficacy of MAVENCLAD on relapse rate and disability progression at five years after starting treatment
- Results from up to 10 years of follow-up from the PREMIERE safety registry, which further support the long-term benefit-risk profile of MAVENCLAD
- New data further illustrating how MAVENCLAD selectively affects key immune cells involved with MS, which may lead to a qualitative change in the immune system
Key Rebif data include:
- Results from an observational study using Nordic registry data, which showed evidence that exposure to IFN β therapies, including Rebif, before and during pregnancy did not affect outcomes at birth
- Results using a new post hoc exploratory statistical methodology, which examined changes in disability status over time using eight years of data from the PRISMS study, demonstrated that early treatment with Rebif was more beneficial on disease progression than delayed treatment
Key evobrutinib data include:
- Three analyses that investigate the potential role of evobrutinib, the first oral, highly selective BTK inhibitor to demonstrate clinical proof of concept in RMS, in inhibiting pathogenic B-cells and promoting myelin repair
Additional Merck activities at ECTRIMS 2019:
- Panel discussion and networking event on 11 September bringing together Patient Advocacy Groups, people living with MS and multi-disciplinary experts to have a conversation about family planning with MS (18:00 – 19:30, Epicenter, Stockholm)
- Daily “Meet the Expert” sessions at Merck booth B40 where different MS experts will share insights from clinical practice with MAVENCLAD, explore family planning for patients with MS and present Merck’s ongoing commitment to MS research and development through the Grant for Multiple Sclerosis Innovation (GMSI)
- Satellite symposium events on 11 September (12:30 – 13:30, Hall A Stockholmsmässan) and 12 September (18:15 – 19:15, Hall A Stockholmsmässan) covering key learnings on disease control in MS, including monitoring methods, recent advancements in MS immune targeting and the importance of innovative registry studies
- #MSInsideOut Experience, including the MS House and virtual reality (VR), at Merck booth B40 that will immerse visitors into a day-in-the-life of an MS patient, educating them on symptoms of MS and how they affect the human body in different settings
Below is a selection of abstracts that have been accepted for presentation at ECTRIMS 2019:
MAVENCLAD® (cladribine tablets) Presentations |
|||
Title |
Authors |
Abstract No. / Poster No. |
Presentation Date/Time/Session |
Reduction of risk of secondary progressive multiple sclerosis within two years of treatment with Cladribine Tablets: An analysis of the CLARITY study |
Vermersch P, Giovannoni G, Soelberg-Sorensen P, Rammohan K, Cook S, Keller B, Roy S |
A-1026-0005-00522 |
Session Title: Poster Session 1 Session Date: 11.09.2019 Presenting Time: 17:15-19:15 h. |
Long-term disease stability assessed by the Expanded Disability Status Scale in patients treated with Cladribine Tablets in the CLARITY and CLARITY Extension studies |
Giovannoni G, Comi G, Rammohan K, Rieckmann P, Vermersch P, Dangond F, Keller B, Jack D |
A-1026-0033-00521 |
ePoster |
The CLARITY Study: Efficacy Outcomes Among Patients Who Received Disease-Modifying Therapies Prior to Treatment with Cladribine Tablets |
Vermersch P, Rammohan K, Damian D, Jack D, Harty G, Wong S L |
A-1026-0031-01868 |
Session Title: Poster Session 1
|
Updated safety of cladribine tablets in the treatment of patients with multiple sclerosis: Integrated safety analysis and post-approval data |
Cook S, Giovannoni G, Leist T, Comi G, Syed S, Nolting A, Damian D, Schick R |
A-1026-0033-00523 |
Session Title: Poster Session 3
|
An analysis of the relationship between cladribine dose and risk of malignancies in patients with multiple sclerosis |
Cook S, Giovannoni G, Leist T, Comi G, Nolting A, Sylvester E, Jack D, Damian D, Galazka A |
A-1026-0033-01927 |
Session Title: Poster Session 1
|
Long term, registry-based, prospective, post-authorization safety study evaluating adverse events of special interest in patients with highly active relapsing multiple sclerosis newly started on oral cladribine − CLARION |
Butzkueven H, Korhonen P, Hillert J, Trojano M, Aydemir A, Magyari M, Khanfir H, Pinuaga C, Sabidó M, CLARION Study group |
A-1026-0033-00518 |
ePoster |
Incidence of any malignancies in patients treated for multiple sclerosis. A Danish registry-based cohort |
Magyari M, Foch C, Nørgaard M, Boutmy E, Veres K, Sabidó M |
A-1026-0034-01799 |
Scientific Session 2: Safety assessment in the post-approval phase - real world evidence
|
Increase of naïve B cells M2 macrophages and reduction of memory B/T cells during immune repopulation at 96 weeks in CLARITY assessed by Immune cell deconvolution |
Giovannoni G, Leist T, Soelberg-Sorensen P, Kalatskaya I, Boschert U, DeMartino J, Rolfe A |
A-1026-0031-00511 |
Session Title: Poster Session 2
|
Long-term effectiveness in patients previously enrolled in the Cladribine Tablets pivotal trials: a Real-World Evidence analysis using data from the Italian Multiple Sclerosis Registry (CLARINET-MS) |
Patti F, Visconti A, Capacchione A, Trojano M on behalf of the CLARINET-MS study group |
A-1026-0031-00516 |
Session Title: Poster Session 1
|
Comparative effectiveness of Cladribine tablets vs other drugs in relapsing-remitting multiple sclerosis: an approach merging randomized controlled trial with real life data |
Signori A, Saccà F, Lanzillo R, Maniscalco GT, Signoriello E, Repice A, Annovazzi P, Baroncini D, Clerico M, Binello E, Cerqua R, Mataluni G, Perini P, Bonavita S, Lavorgna L, Zarbo IR, Laroni A, Gutierrez LP, Gioia SL, Frigeni B, Barcella V, Frau J, Cocco E, Fenu G, Clerici VT, Sartori A, Rasia S, Cordioli C, Stromillo ML, Di Sapio A, Pontecorvo S, Grasso R, Barone S, Barrilà C, Russo CV, Esposito S, Ippolito D, Landi D, Visconti A, Sormani MP |
A-1026-0031-00187 |
Session Title: Poster Session 2
|
CD4+ T cells and CD19+ B cells respond differentially to cladribine treatment in vitro depending on their activation status. Role of deoxycytidine kinase |
Carlini F, Ivaldi F, Boschert U, Visconti A, de Rosbo NK, Uccelli A |
P1353 |
Session Title: Poster Session 3
|
Studying the effect of cladribine on microglia survival, proliferation, activation and cytokine release |
Eixarch H, Calvo-Barreiro L, Fissolo N, Boschert U, Comabella M, Montalban X, Espejo C |
P610 |
Session Title: Poster Session 1
|
Effects of 2-chlorodeoxyadenosine (Cladribine) on Microglial cells and Astrocytes |
Aybar F, Perez MJ, Pasquini JM, Correale J |
P623 |
Session Title: Poster Session 1
|
Understanding the mechanisms of action of Cladribine in innate immune cells in MS |
C. Rodríguez-Mogeda, S. Van der Pol, A.J. Van het Hof, HE. De Vries |
P984 |
Session Title: Poster Session 2
|
Year 1 Performance of adveva®, a Patient Support Programme for patients taking MAVENCLAD (cladribine tablets) in UK |
Lyons M, Lott N, Morgan K |
A-1026-0037-01914 |
ePoster |
Cladribine is not mutagenic to mitochondrial DNA and RNA in leukemic cell lines |
Järvinen E, Tienari PJ, Battersby BJ |
P698 |
Session Title: Poster Session 1
|
Cladribine modify functional properties of murine microglia |
Jørgensen LØ, Hyrlov KH, Elkjær ML, Pedersen AE, Svenningsen ÅF, Illes Z |
A-1026-0031-01729 |
Session Title: Poster Session 2
|
Safety data from the non-interventional, prospective study CLEVER (CLadribine Tablets – EValuation of thERapy satisfaction) and CLADQoL (CLADribine Tablets – evaluation of Quality of Life) |
Penner, I-K, Ziemssen T, Nolting A, Hübschen M, Richter J, Schel E, Wagner T, Mueller B, Posevitz-Fejfar A |
A-1026-0031-01026 |
Session Title: Poster Session 1
|
Non-interventional, prospective study CLEVER (CLadribine Tablets – EValuation of thERapy satisfaction) |
Ziemssen T, Grothe C, Reifschneider G, Morgenbesser T, Richter J, Schel E, Wagner T, Müller B, Posevitz-Fejfar A |
A-1026-0031-01164 |
Session Title: Poster Session 1
|
Non-interventional, prospective study CLADQoL (CLADribine Tablets - evaluation of Quality of Life) |
Penner, I-K, Raji A, Pul R, Kallmann BA, Richter J, Schel E, Wagner T, Müller B, Posevitz-Fejfar A |
A-1026-0031-01120 |
ePoster |
Cladribine tablets versus other disease-modifying oral treatments in multiple sclerosis (MS) in achieving no evidence of radiological and clinical disease activity (NEDA) - network meta-analysis (NMA) |
Bartosik-Psujek H, Kaczyński Ł, Górecka M, Rolka M, Wójcik R, Kaczor M P ,Zięba P |
A-1026-0037-01912 |
Session Title: Poster Session 2
|
Cladribine tablets: Observational evaluation of effectiveness, safety, and patient reported outcomes in suboptimally controlled patients previously taking injectable disease-modifying drugs for relapsing forms of multiple sclerosis (CLICK-MS) |
Miravalle A A, Katz J, Sloane J, Hayward B, Walsh J S, Harlow D E |
A-1026-0033-01906 |
ePoster |
Risk reduction of EDSS progression in patients with relapsing multiple sclerosis treated with cladribine tablets in the CLARITY study: post-hoc analysis including patients who went on to receive rescue therapy |
Thrower B, Fox E J, Damian D, Lebson L, Dangond F |
A-1026-0031-01938 |
Session Title: Poster Session 1
|
In depth analysis of B cells in multiple sclerosis patients after treatment with cladribine |
Marsh-Wakefield F, Juillard P, Ashhurst T, McGuire H, Byrne SN, Hawke S, Grau GE |
P1225 |
Session Title: Poster Session 3
|
FIMS Study: Exploration of Factors which Influence treatment decisions of patients with Multiple Sclerosis |
Bardsley B, Cinc E, Heriot E, Lazarus K-J, McMurtrie M, Haynes J, Coleman E, Macdonell R |
P676 |
Session Title: Poster Session 1
|
Markers of premature immunosenescence in the peripheral blood of multiple sclerosis subjects vs. healthy controls |
Clénet ML, Daigneault A, Laurent C, Jamann H, Mamane V, Ouedraogo O, Carmena Moratalla A, Duquette P, Rousseau MC, Arbour N and Larochelle C |
A-1026-0029-01320 |
Session Title: Poster Session 1
|
MAVENCLAD® (cladribine tablets) Late-Breaker Presentation |
|||
Cladribine decreases CD95 expressing CD4+ and CD8+ cells in lymphoid organs in naïve marmosets (Callithrix jacchus) |
Kap Y, Boschert U, t'Hart B |
A-1026-0000-02694 |
Session Title: Poster Session 3 Session Date: 13.09.2019 Presenting Time: 12:15-14:15 |
Rebif® (interferon beta-1a) Presentations |
|||
Effect of Interferon β-1a Treatment on Serum Neurofilament Light Chain Levels in Patients with a First Clinical Demyelinating Event in the REFLEX trial |
Kuhle J, Leppert D, Comi G, De Stefano N, Kappos L, Freedman MS, Roy S, Issard D |
A-1026-0035-00622 |
Session Title: Poster Session 3
|
Pharmacodynamic biomarkers of interferon β-1a: Assessment in patients receiving long-term treatment with subcutaneous interferon β-1a in REFLEX and REFLEXION |
Freedman MS, Wojcik J, D’Antonio M, Hyvert Y, Stinchi S, D’Urso V, Dangond F |
A-1026-0033-00634 |
Session Title: Poster Session 3
|
Efficacy of subcutaneous interferon β-1a in patients with a first clinical demyelinating event: the REbif FLEXible dosing in early multiple sclerosis (REFLEX) study – outcomes in patients stratified by the 2017 McDonald criteria |
Freedman MS, Kappos L, Comi G, De Stefano N, Roy S, Issard D |
A-1026-0031-00626 |
Session Title: Poster Session 3
|
Post-hoc Analysis to Evaluate the Effects of Subcutaneous Interferon β-1a in Subgroups of Patients from the PRISMS Study with Early Onset vs Late Onset Disease |
Freedman MS, Brod S, Wray S, Singer B, Dangond F, Issard D, Harlow D, Jack D |
A-1026-0031-00628 |
ePoster |
Assessing the duration of EDSS improvement after a therapy start: a new statistical approach applied to the long term extension of the PRISMS study |
Signori A, Bovis F, Carmisciano L, Alexandri N, Sormani M P |
A-1026-0035-00443 |
Session Title: Poster Session 3
|
Effectiveness of subcutaneous interferon beta-1a 22/44 μg versus teriflunomide in newly treated patients with multiple sclerosis. A study in a French nationwide cohort of Multiple Sclerosis: Observatoire Francais de la sclérose en plaques (OFSEP) |
Rollot F, Foch C, Laplaud D, Boutmy E, Marhardt K, Sabido S |
A-1026-0034-00636 |
Session Title: Poster Session 2
|
Prevalence of infant outcomes at birth after exposure to interferon beta prior to or during pregnancy: A register-based cohort study in Finland and Sweden among women with MS |
Vattulainen P, Burkill S, Geissbuehler Y, Sabidó M, Popescu C, Adamo A, Myhr K-M, Montgomery S, Korhonen P, the European Interferon Beta Pregnancy Study Group and the Nordic MS Pregnancy & Interferon Beta study group |
A-1026-0009-01725 |
Session Title: Poster Session 3
|
Systematic mapping of the global educational offerings for multiple sclerosis patients on the topic of disease progression |
Bharadia T, Kesselring J, Boyko A, Sumelahti M-L on behalf of the MS in the 21st Century initiative, and Alexandri N |
A-1026-0005-01837 |
Session Title: Poster Session 2
|
Family planning decisions in people with multiple sclerosis |
Lavorgna L, Worton H, S Russell, Jack D |
A-1026-0009-00639 |
Session Title: Poster Session 3
|
Evobrutinib (Bruton’s Tyrosine Kinase Inhibitor) Presentations |
|||
Bruton’s tyrosine kinase (BTK) inhibition promotes myelin repair in two different models of demyelination |
Aigrot M S, Martin E, Grenningloh R, Stankoff B, Lubetzki C, Boschert U, Zalc B |
A-1026-0025-01553 |
Session Title: Poster Session 3
|
Inhibition of Bruton’s Tyrosine Kinase Selectively Prevents Antigen-Activation of B cells and Ameliorates B cell-Mediated Experimental Autoimmune Encephalomyelitis |
Torke S, Häusler D, Grenningloh R, Boschert U, Brück W and Weber M S |
A-1026-0031-01785 |
Session Title: Poster Session 2
|
Effect of evobrutinib, a Bruton’s tyrosine kinase inhibitor, on immune cell and immunoglobulin levels over 48 weeks in a phase 2 study in relapsing multiple sclerosis |
Montalban X, Shaw J, Syed S, Dangond F, Martin E C, Grenningloh R, Weber MS, on behalf of the Evobrutinib Phase 2 Study Group |
A-1026-0031-01645 |
Session Title: Poster Session 3
|
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 more than 60 countries, including Canada, Australia and the U.S.
The clinical development program 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), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). 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. BTK inhibition is thought to suppress autoantibody-producing cells, which preclinical research suggests may be therapeutically useful in certain autoimmune diseases. 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 2.3 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, with a robust pipeline focusing on discovering new therapies that have the potential to modulate key pathogenic mechanisms in MS. Merck aims to improve the lives of those living with MS, by addressing areas of unmet medical needs.
The company's robust immunology pipeline focuses on discovering new therapies that have the potential to modulate key pathogenic mechanisms in chronic diseases such as MS, systemic lupus erythematosus (SLE) and forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).
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.
About Merck
Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 52,000 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 2018, Merck generated sales of € 14.8 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 Performance Materials.
