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

Darmstadt (Germany) October 18th (PROTEXT/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®(Cladribine Tablets) and Rebif® (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® 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® which further 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'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 €1,000,000 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 or #AddressMS) or visit booth 08.

The following MAVENCLAD® and Rebif® 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®

MAVENCLAD® (cladribine tablets) is approved in the European Union for the treatment of highly active relapsing multiple sclerosis[*] (RMS). 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). MAVENCLAD® 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® 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® 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® 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® 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®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® 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®. 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® (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® 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® 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® in year 1,

- before initiating MAVENCLAD® in year 2,

- 2 and 6 months after start of treatment in each treatment year. If the lymphocyte count is below 500 cells/mm3, 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/mm3, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia. Interruption or delay of MAVENCLAD® 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® (usually within 3 months).

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 administrated 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 RebiSlideTM. 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.

Rebif® (interferon beta-1a) is approved in the United States for relapsing forms of MS. RebiSmart®, an electronic device for self-injection of Rebif®, 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 € 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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Source: Merck