New Data to be Presented on MS Portfolio, Rebif (interferon beta-1a), Cladribine Tablets, and Evobrutinib at ECTRIMS 2017

 

Important safety and immune cell analyses further characterize the selective immune reconstitution approach of Cladribine Tablets

Continued innovation with Rebif includes analysis of NEDA and use of MAGNIMS criteria in predicting clinical outcomes out to 15 years

Pre-clinical data for investigational evobrutinib highlight potential role in patients with relapsing MS 

A total of 40 abstracts will be presented by lead investigators

 

Darmstadt, Germany, October 18, 2017 – Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced that data for approved multiple sclerosis (MS) treatment Rebif® (interferon beta-1a) and for investigational MS treatments Cladribine Tablets and evobrutinib will be presented at MSParis 2017, 7th Joint ECTRIMS-ACTRIMS Meeting, 25-28 October 2017 in Paris, France. Efficacy data will be presented from the CLARITY, CLARITY Extension and ORACLE-MS trials which highlight that Cladribine Tablets may have certain clinical benefits up to 4 years with a maximum of 20 days of oral treatment in the first 2 years. Additional safety analysis demonstrate that that there was no statistically significant difference in malignancy risk between Cladribine Tablets and placebo. Additional data for Cladribine Tablets detail how the treatment is thought to selectively target the adaptive immune system.

Data presentations for Rebif® will focus on long-term disease activity assessed by the MAGNIMS (Magnetic Resonance Imaging in MS) score. Real-world evidence presentations will evaluate relapse rates in patients newly initiating on Rebif®, and an assessment of treatment adherence rates for patients treated with Rebif® compared with dimethyl fumarate.

Furthermore, key preclinical data will be presented for Merck KGaA, Darmstadt, Germany’s investigational evobrutinib (M2951), a Bruton’s tyrosine kinase (BTK) inhibitor, which is thought to be important in the development and functioning of various immune cells including B lymphocytes, specifically in patients with MS.

“The breadth of data being presented at this year’s congress underpin our commitment to deepening the understanding of how our portfolio of products, whether approved or investigational, target MS, and reinforce our dedication to provide differentiated treatment options to physicians and people living with MS,” said Luciano Rossetti, Head of Global R&D for the biopharma business of Merck KGaA, Darmstadt, Germany.

In addition to data presentations, two Merck KGaA, Darmstadt, Germany-sponsored symposia will take place during the meeting:

  • - Balancing benefits and risks of DMDs in MS, Thursday, October 26, 18:00-19:00, Hall A
  • - Potential solutions to treatment burden in MS, Friday, October 27, 08:00-09:00, Hall A

On Wednesday, October 25, from 9:30-11:30am CEST, Merck KGaA, Darmstadt, Germany will be hosting a press event briefing with members of the leadership team and lead investigators. A link to view this event will be available for media offsite, please contact erinmarie.beals@emdserono.com for further information. This event is not intended for US media. Additionally, at 19:30pm CEST, Merck KGaA, Darmstadt, Germany will be hosting a session highlighting data from a report which will be published during MSParis 17 entitled, Addressing the Socio-economic impact of Multiple Sclerosis on Women in Europe. 

On Thursday, October 26, Merck KGaA, Darmstadt, Germany will also be hosting the annual Grant for Multiple Sclerosis Innovation (GMSI) Award Event at the Palais des Congres, Havane Theatre. The award, first launched at ECTRIMS in 2012, supports the advancement of science and medical research in the field of MS, and provides a grant of up to €1,000,000 per year to one or more selected research projects. 

On Friday, October 27, MS in the 21st Century (a Merck KGaA, Darmstadt, Germany sponsored initiative involving a joint Steering Group of international healthcare professionals and MS patient advocates) will host their first educational workshop titled ‘Two monologues do not make a dialogue – Overcoming communications barriers between healthcare professionals and patient’, to encourage better communication between healthcare professionals and people with MS. 

For up-to-date information and activities during ECTRIMS 2017, follow Merck KGaA, Darmstadt, Germany on Twitter (@EMDGroup) or #AddressMS or visit booth 08.

The following Cladribine Tablets and Rebif® global abstracts have been accepted for presentation at MSParis 2017, 7th Joint ECTRIMS-ACTRIMS Meeting:

Title

Lead Author

Abstract/Poster #

Presentation Date/Time/Session

Cladribine Tablets Presentations

Effects of Cladribine Tablets on CD4+ T Cell Subsets in the ORACLE-MS Study: Results from an Analysis of Lymphocyte Surface Markers

Stuve O P667

Poster Session 1
Thursday 26 October 2017
Time: 15:30-17:00

Cladribine Tablets Produce Selective and Discontinuous Reduction of B and T Lymphocytes and Natural Killer Cells in Patients with Early and Relapsing Multiple Sclerosis (ORACLE-MS,CLARITY and CLARITY Extension) Stuve O P690
Rates of Lymphopenia Year-by-year in Patients with Relapsing Multiple Sclerosis Treated and Retreated with Cladribine Tablets 3.5mg/kg Cook S P666
Long-Term Lymphocyte Counts in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Treated with Cladribine Tablets 3.5 mg/kg: Total Lymphocytes, B and T Cell Subsets Soelberg-Sorensen P P655
Effects of Cladribine Tablets on Radiological Outcomes in High Disease Activity (HDA) Subgroups of Patients with Relapsing Multiple Sclerosis (RMS) in the CLARITY Study Giovannoni G P1164 Poster Session 2
Friday 27 October 2017
Time: 15:30-17:00
Proportions of Patients with Highly Active RMS Achieving No Evidence of Disease Activity (NEDA) in Response to Cladribine Tablets in CLARITY Giovannoni G P1143
Investigation of Cladribine Treatment Rules in Subjects with Relapsing-Remitting Multiple Sclerosis (RRMS) by means of Modelling & Simulation Terranova N P912
Infections During Periods of Grade 3 or 4 Lymphopenia in Patients Taking Cladribine Tablets 3.5 mg/kg: Data from an Integrated Safety Analysis Cook S P1142
Innate Immune Cell Counts in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Treated with Cladribine Tablets 3.5 mg/kg in CLARITY and CLARITY Extension Soelberg-Sorensen P P1141
An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis (RMS) Galazka A P1878

Late-breaker

Poster Session 2
Friday 27 October 2017
Time: 15:30-17:00

Pregnancy outcomes during the clinical development programme of cladribine in multiple sclerosis (MS): an integrated analysis of safety for all exposed patients Galazka A P1874

 

Rebif (interferon beta-1a) Presentations

Title Lead Author Abstract/Poster # Presentation Date/Time/Session
Disease Activity as Assessed by the MAGNIMS Score Predicts Long-Term Clinical Disease Activity Free Status and Disability Progression in Patients Treated with Subcutaneous Interferon Beta-1a Sormani MP P770 Poster Session 1
Thursday 26 October 2017
Time: 15:30-17:00
The Association between Disease Activity and Disability Progression in Patients with Relapsing-Remitting Multiple Sclerosis Spelman T P348
Clinical Characteristics and Treatment Patterns of Relapsing-Remitting Multiple Sclerosis Patients with High Disease Activity Spelman T P340
Comparing patient and healthcare professional perceptions on multiple sclerosis management and care where do their priorities differ? Results from a qualitative survey Rieckman P P814
Infertility Diagnosis and Treatment in Women With and Without Multiple Sclerosis Houtchens MK P356
Validation of MUSIQOL among Arabic-speaking MS Patients treated with High dose INF-β 1a sc injection New Formulation Al Jumah M P821
RebiQoL: A telemedicine patient support program on health related quality of life and adherence in MS patients treated with Rebif Landtblom AM P826
Serum Neurofilament light chain correlates with disease activity and predicts clinical and MRI outcomes in MS Barro C P636
Impact of the Presence of Gadolinium-Enhancing Lesions at Baseline on No Evidence of Disease Activity Status in Patients Treated with Subcutaneous Interferon Beta-1a: A Post-Hoc Analysis of REFLEXION Freedman M P1144 Poster Session 2
Friday 27 October 2017
Time: 15:30-17:00
Evolution of New Lesions and its Temporal Patterns in Patients with Clinically Isolated Syndrome Treated with Subcutaneous Interferon Beta-1a Vrenken H P1025
Using algorithms to identify High Disease Activity Relapsing-Remitting Multiple Sclerosis patients using electronic health record data with natural language processing Kamauu AW P877
Using United States Integrated Delivery Network (IDN) Electronic Health Records (EHR)/Natural Language Processing (NLP)-Based Algorithms to Identify Relapses in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients Kamauu AW P885
Developing United States Integrated Delivery Network (IDN) Claims-Based Algorithms to Identify Relapses in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients Kamauu AW P878
Rates of Pregnancy in Women With and Without Multiple Sclerosis Over Time Houtchens MK P890
Prevalence of Comorbidities in Patients With and Without Multiple Sclerosis by Age and Sex: A US Retrospective Claims Database Analysis Kresa-Reahl K P941
Infertility Treatment and Live Birth Rates in Women With and Without Multiple Sclerosis Houtchens MK P891
An Evaluation of Adherence Using Panel Survey Data From Patients With Multiple Sclerosis Treated With Subcutaneous Interferon β-1a or Dimethyl Fumarate Perrin Ross A P1251
Real-World Assessment of Relapse in Patients With Multiple Sclerosis Newly Initiating scIFNβ1a Compared With Oral Disease-Modifying Drugs Bowen J P1245
Interferon-beta and regulatory cells: evaluation of treatment-induced modulation of Treg, Breg and CD56bright NK cell levels in multiple sclerosis patients Martire S P1140
Risk of stroke in patients with multiple sclerosis treated with subcutaneous interferon beta-1a Venkatesh S P1918

Late-breaker

Poster Session 2
Friday 27 October 2017
Time: 15:30-17:00

Creating a healthcare claims-based adaptation of Kurtzke Functional Systems Scores for assessing multiple sclerosis severity and progression Le Truong CTL EP1767 ePoster
A mapping study to compare the educational offerings for patients in the fields of multiple sclerosis and HIV in Europe and Canada Rieckman P EP1838
Long-term real-life retrospective analysis on interferon β1-a use in RRMS patients in Finland Al Jumah M EP1687
Adherence, cognition and behavioral performance in relapsing-remitting MS (RRMS) patients using the electronic autoinjector RetainSmartTM: 1 and 2 year follow-up from the German multicenter RETAINsmart study Rau D EP1692
Cerebrospinal fluid levels of neurofilament light chain, C-X-C ligand motif 13, and chitinase-3-like protein 1 reflect distinct pathological processes in multiple sclerosis Zanoni M EP1598
Brain atrophy and disease free status over 3 years in multiple sclerosis patients under interferon beta 1a subcutaneous treatment Rojas JI EP1657

 

Evobrutinib Presentations

Title Lead Author Abstract/Poster #  Presentation Date/Time/Session
B cell-mediated experimental CNS autoimmunity is modulated by inhibition of Bruton’s tyrosine kinase Torke S 143 Oral Presentation
Parallel Session 8: Immune Cells in Injury and Repair
Thursday 26 October 2017
14:00-15:30
Design of a Phase II Dose Range Finding, Efficacy and Safety Study of the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib (M2951) in Relapsing Multiple Sclerosis Patients Montalban X P675 Poster Session 1
Thursday 26 October 2017
Time: 15:30-17:00
T cell mediated experimental CNS autoimmunity induced by PLP in SJL mice is modulated by Evobrutinib (M2951) a novel Bruton’s tyrosine kinase inhibitor Boschert U P678

 

About Cladribine Tablets
Cladribine Tablets is an investigational short-course oral therapy that is thought to selectively and periodically target lymphocytes thought to be integral to the pathological process of relapsing MS (RMS). Cladribine Tablets is currently under clinical investigation and not yet approved for the treatment for any use in the United States and Canada. In August 2017, the European Commission (EC) granted marketing authorization for Cladribine Tablets, marketed as MAVENCLAD® in the European Union (EU), for the treatment of relapsing forms of multiple sclerosis (RMS) in the 28 countries of the EU in addition to Norway, Liechtenstein and Iceland.
 
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 two-year Phase III placebo-controlled study following on from the CLARITY study, designed to evaluate the safety and efficacy of Cladribine Tablets over an extended administration for four years.
  • - 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 Patients Who Have Participated in Cladribine Clinical Studies) study: interim long-term follow-up data from the prospective registry, PREMIERE, to evaluate the safety and efficacy of Cladribine Tablets. This includes more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program, and more than 10 years of observation in some patients. 
 
About Rebif® (interferon beta-1a) 
Rebif (interferon beta-1a) is used to treat relapsing forms of MS to decrease the frequency of relapses and delay the occurrence of some of the physical disability that is common in people with MS. The efficacy and safety of Rebif in controlled clinical trials beyond 2-years has not been established. 
 
Important Safety Information:
Rebif is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation. 
 
Rebif should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression, suicidal ideation, and suicide attempts have been reported to occur with increased frequency in patients receiving interferon compounds, including Rebif. 
 
Severe liver injury, including some cases of hepatic failure requiring liver transplantation, has been reported rarely in patients taking Rebif. The potential for liver injury should be considered when used in combination with other products associated with liver injury.  Monitor liver function tests and patients for signs and symptoms of hepatic injury.  Consider discontinuing Rebif if hepatic injury occurs.
 
Anaphylaxis and other allergic reactions (some severe) have been reported as a rare complication of Rebif. Discontinue Rebif if anaphylaxis occurs. 
 
In controlled clinical trials, injection site reactions occurred more frequently in Rebif-treated patients than in placebo-treated and Avonex-treated patients. Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting. Do not administer Rebif into affected area until fully healed; if multiple lesions occur, discontinue Rebif until skin lesions are healed. 
 
Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in Rebif-treated patients. In controlled clinical trials, leukopenia occurred at a higher frequency in Rebif-treated patients than in placebo and Avonex-treated patients. Thrombocytopenia and anemia occurred more frequently in 44 mcg Rebif-treated patients than in placebo-treated patients. Patients should be monitored for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended. 
 
Cases of thrombotic microangiopathy (TMA), some fatal, have been reported with interferon beta products, including Rebif, up to several weeks or years after starting therapy. Discontinue Rebif if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.
 
Caution should be exercised when administering Rebif to patients with pre-existing seizure disorders. Seizures have been temporally associated with the use of beta interferons, including Rebif, in clinical trials and in postmarketing reports. 
 
The most common side effects with Rebif are injection-site disorders, headaches, influenza-like symptoms, abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities. 
 
There are no adequate and well-controlled studies in pregnant women. Rebif should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
 
 
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 in Phase II studies. 
 
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.
 
All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service. 
 
 
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. Around 50,000 employees work to further develop technologies that improve and enhance life – from biopharmaceutical therapies to treat cancer or multiple sclerosis, cutting-edge systems for scientific research and production, to liquid crystals for smartphones and LCD televisions. In 2016, Merck KGaA, Darmstadt, Germany, generated sales of € 15.0 billion in 66 countries.
Founded in 1668, Merck KGaA, Darmstadt, Germany, is the world's oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck KGaA, Darmstadt, Germany, holds the global rights to the „Merck” name and brand. The only exceptions are the United States and Canada, where the company operates as EMD Serono, MilliporeSigma and EMD Performance Materials.
 

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