Merck to Present New Data on MS Portfolio: Rebif, Mavenclad, and Evobrutinib at ECTRIMS 2017

DARMSTADT, Germany, October 18, 2017/PRNewswire/ —

Not intended for US/UK based media

Merck to Present New Data on MS Portfolio: Rebif, Mavenclad, and
Evobrutinib at ECTRIMS 2017

— Important safety and immune cell analyses further characterize the selective immune reconstitution approach of Mavenclad  — 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

Merck, a leading science and technology company, today announced that data for approved and investigational multiple sclerosis (MS) treatments, MAVENCLAD(R)(Cladribine Tablets) and Rebif(R) (interferon beta-1a) 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 MAVENCLAD(R) delivers and sustains 4 years of disease control with a maximum of 20 days of oral treatment in the first 2 years. Additional safety analysis assessing malignancy and infection risk will be presented along with data for MAVENCLAD(R)  which further detail how the treatment is thought to selectively target the adaptive immune system.

Data presentations for Rebif(R) 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(R), and an assessment of treatment adherence rates for patients treated with Rebif(R) compared with dimethyl fumarate.

Furthermore, key preclinical data will be presented for Merck’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 Merck’s 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.

In addition to data presentations, two Merck-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 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 ectrimspressevent@merckgroup.com for further information. Additionally, at 19:30pm CEST, Merck 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 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 EUR1,000,000 per year to one or more selected research projects.

On Friday, October 27, MS in the 21st Century (Merck 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. As part of this workshop, two new communication tools will also be launched: ‘my/MS Priorities’ and ‘my/MS Commitments’, both of which are designed to be used jointly with people with MS and their healthcare team to improve the quality and efficiency of clinical consultations and disease management.

For up-to-date information and activities during ECTRIMS 2017, follow Merck on Twitter (@MerckHealthcare [https://twitter.com/MerckHealthcare ] or #AddressMS) or visit booth 08.

The following MAVENCLAD(R) and Rebif(R) global abstracts have been accepted for presentation at MSParis 2017, 7th Joint ECTRIMS-ACTRIMS Meeting:

MAVENCLAD (Cladribine Tablets) Presentations                                                 Abstract/       Presentation    Title                      Lead Author       Poster #        Date/Time/Session    Effects of Cladribine    Tablets on CD4+ T Cell    Subsets in the ORACLE-MS                                     Poster Session 1    Study: Results from an                                       Thursday 26 October    Analysis of Lymphocyte                                       2017    Surface Markers            Stuve O           P667            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  Soelberg-Sorensen    Subsets                    P                 P655                                                                                                                                                                                                   Effects of Cladribine                                        Poster Session 2    Tablets on Radiological                                      Friday 27 October 2017    Outcomes in High Disease                                     Time: 15:30-17:00    Activity (HDA) Subgroups                                         of Patients with Relapsing                                   Poster Session 2    Multiple Sclerosis (RMS)                                     Friday 27 October 2017    in the CLARITY Study       Giovannoni G      P1164           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        Soelberg-    Extension                  Sorensen P        P1141                              An analysis of malignancy                                    Late-breaker    risk in the clinical                                         Poster Session 2                                           development programme of                                     Friday 27 October 2017    cladribine tablets in                                        Time: 15:30-17:00    patients with relapsing    multiple sclerosis (RMS)   Galazka A         P1878                                                                                                                                                                                                             Pregnancy outcomes during                                    Late-breaker    the clinical development                                     Poster Session 2    programme of cladribine in                                   Friday 27 October 2017    multiple sclerosis (MS):                                     Time: 15:30-17:00    an integrated analysis of    safety for all exposed    patients                   Galazka A         P1874               Rebif (interferon beta-1a) Presentations                                                 Abstract/       Presentation    Title                      Lead Author       Poster #        Date/Time/Session                                                                                                                                                                                                      Disease Activity as                                          Poster Session 1                                    Assessed by the MAGNIMS                                      Thursday 26 October    Score Predicts Long-Term                                     2017    Clinical Disease Activity                                    Time: 15:30-17:00    Free Status and Disability                                   Poster Session 1    Progression in Patients                                      Thursday 26 October    Treated with Subcutaneous                                    2017    Interferon Beta-1a         Sormani MP        P770            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      AP356    Validation of MUSIQOL    among Arabic-speaking MS    Patients treated with High    dose INF-beta 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                                    Poster Session 2                          Gadolinium-Enhancing                                         Friday 27 October 2017    Lesions at Baseline on No                                    Time: 15:30-17:00    Evidence of Disease                                          Poster Session 2    Activity Status in                                           Friday 27 October 2017    Patients Treated with                                        Time: 15:30-17:00    Subcutaneous Interferon    Beta-1a: A Post-Hoc    Analysis of REFLEXION      Freedman M        P1144               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 beta-1a or    Dimethyl Fumarate          Perrin Ross A     P1251    Real-World Assessment of    Relapse in Patients With    Multiple Sclerosis Newly    Initiating scIFNbeta1a    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                                   Late-breaker    with multiple sclerosis                                      Poster Session 2    treated with subcutaneous                                    Friday 27 October 2017    interferon beta-1a         Venkatesh S       P1918           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          ePosters    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 beta1-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                                                 Abstract/       Presentation    Title                      Lead Author       Poster #        Date/Time/Session                                                                                                                              Oral Presentation    B cell-mediated                                              Parallel Session 8:                              experimental CNS                                             Immune Cells in Injury    autoimmunity is modulated                                    and Repair    by inhibition of Bruton’s                                    Thursday 26 October 2017    tyrosine kinase            Torke S           143             14:00-15:30                                                                     Design of a Phase II Dose                                    Poster Session 1    Range Finding, Efficacy                                      Thursday 26 October 2017    and Safety Study of the                                      Time: 15:30-17:00                             Bruton’s Tyrosine Kinase                                         Inhibitor Evobrutinib    (M2951) in Relapsing    Multiple Sclerosis    Patients                   Montalban X       P675                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 MAVENCLAD(R)
MAVENCLAD(R) (cladribine tablets) is approved in the European Union for the treatment of highly active relapsing multiple sclerosis[*] (RMS). MAVENCLAD(R) is a short-course oral therapy that selectively and periodically targets lymphocytes thought to be integral to the pathological process of relapsing MS (RMS). MAVENCLAD(R) is currently under clinical investigation and not yet approved for the treatment for any use in the United States or Canada. In August 2017, the European Commission (EC) granted marketing authorization for
MAVENCLAD(R) 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.

The clinical development program for MAVENCLAD(R) 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 MAVENCLAD(R) 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 MAVENCLAD(R)  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 MAVENCLAD(R)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 MAVENCLAD(R) 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 MAVENCLAD(R). 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.

EU Indication
MAVENCLAD(R) (cladribine tablets) is indicated for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS) as defined by clinical or imaging features.

Important EU Safety Information
Contraindications:
MAVENCLAD(R) is contraindicated in patients with hypersensitivity to the active substance, human immunodeficiency virus (HIV), active chronic infection (tuberculosis or hepatitis), active malignancy, moderate to severe renal impairment (creatinine clearance <60 mL/min), and those who are pregnant and breast-feeding. MAVENCLAD(R) is also contraindicated in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy.

Special warnings and precautions for use:

The most clinically relevant adverse reactions were lymphopenia and herpes zoster.

Haematological monitoring

Decreases in neutrophil count, red blood cell count, haematocrit, haemoglobin or platelet count compared to baseline values have been observed in clinical studies, although these parameters usually remain within normal limits.

Additive haematological adverse reactions may be expected if cladribine is administered prior to or concomitantly with other substances that affect the haematological profile

Lymphocyte counts must be determined

— before initiating MAVENCLAD(R) in year 1,- before initiating MAVENCLAD(R) in year 2,- 2 and 6 months after start of treatment in each treatment year. If the lymphocyte count is below 500 cells/mmcubed, it should be actively monitored until values increase again.

Infections
Cladribine can reduce the body’s immune defence and may increase the likelihood of infections. HIV infection, active tuberculosis and active hepatitis must be excluded before initiation of cladribine.

The incidence of herpes zoster was increased in patients on cladribine. If lymphocyte counts drop below 200 cells/mmcubed, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia. Interruption or delay of MAVENCLAD(R) may be considered until proper resolution of the infection.

Cases of progressive multifocal leukoencephalopathy (PML) have been reported for parenteral cladribine in patients treated for hairy cell leukaemia with a different treatment regimen.

In the clinical study data base of cladribine in MS (1,976 patients, 8,650 patient years) no case of PML has been reported. However, a baseline magnetic resonance imaging (MRI) should be performed before initiating MAVENCLAD(R) (usually within 3 months).

About Rebif(R)
Rebif(R) (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(R) in chronic progressive MS has not been established. Interferon ss is thought to help reduce inflammation. The exact mechanism is unknown.

Rebif(R), which was approved in Europe in 1998 and in the US in 2002, is registered in more than 90 countries worldwide. Rebif(R) has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area[+].

Rebif(R) can be administrated with the RebiSmart(R) electronic auto-injection device (not approved in the US), or with the RebiDose(R) single-use disposable pen, or the manual multidose injection pen RebiSlide(TM). Rebif(R) can also be administered with the autoinjector Rebiject II(R) 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(R) in early multiple sclerosis. The extension of the indication of Rebif(R)has not been submitted in the United States.

Rebif(R) 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(R) with their doctors.

Rebif(R) (interferon beta-1a) is approved in the United States for relapsing forms of MS.  RebiSmart(R), an electronic device for self-injection of Rebif(R), is also not approved in the United States. Cladribine Tablets is an investigational product and not approved for use in any indication in the United States.

[+]The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

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.

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About Merck
Merck 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 generated sales of EUR 15.0 billion in 66 countries.

Founded in 1668, Merck is the world’s oldest pharmaceutical and chemical company. The founding family remains the majority owner of the publicly listed corporate group. Merck 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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