New Efficacy and Safety Data on MS Portfolio to Be Presented at ECTRIMS 2018
DARMSTADT, Germany, Oct. 8, 2018 /PRNewswire/ --
-- Late-breaking Phase II primary endpoint data for investigational therapy
evobrutinib, the first oral BTK inhibitor to show clinical
proof-of-concept in RMS
-- Up to 10 years of patient experience provides further insight into the
benefit-risk profile of investigational cladribine tablets
-- Late-breaking data from multi-sponsored European IFN Pregnancy registry
highlight Rebif safety outcomes during pregnancy
-- A total of 23 abstracts for cladribine tablets, Rebif and evobrutinib
will be presented at ECTRIMS 2018
Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced that it will present data from approved and investigational multiple sclerosis (MS) treatments from its neurology and immunology portfolio at the 34(th) Congress of the European Committee for Treatment and Research In Multiple Sclerosis (ECTRIMS), taking place from 10-12 October 2018, in Berlin, Germany. Merck KGaA, Darmstadt, Germany will present 23 abstracts, including new safety and efficacy data on investigational cladribine tablets, Rebif(®) (interferon beta-1a) and investigational therapy evobrutinib, a highly-specific, oral Bruton's Tyrosine Kinase (BTK) inhibitor.
Key cladribine tablets data will include:
-- An updated integrated safety analysis of patients from the CLARITY,
CLARITY Extension and ORACLE-MS trials, including two additional years
of data from the long-term PREMIERE Registry (up to 10-years of
follow-up).
-- An overview of the first six months of real-world evidence safety data
on cladribine tablets.
-- Results from a post hoc analysis of the CLARITY study will characterize
relapse severity and frequency in relapsing-remitting MS (RRMS) patients
in cladribine tablets versus placebo.
-- New data from post hoc analyses to support the duration of effect of
cladribine tablets across patient subgroups of different ages and with
different disease activity status (in Years 3 and 4 post-treatment) will
be presented.
Key late-breaking data presentations include:
-- Results of primary 24-week MRI endpoint analysis, along with a
description of interim key secondary and safety analysis from a Phase II
study of investigational BTK-inhibitor evobrutinib in patients with
relapsing MS. The late-breaking oral presentation will highlight the
first evidence of clinical activity of a BTK-inhibitor in a non-oncology
indication.
-- Presentation highlighting pregnancy and infant outcomes with multiple
IFN therapies, including Rebif(®), from the European IFN pregnancy
registry and Nordic health registers.
"We are proud to be presenting new data across our Neurology and Immunology franchise at Merck KGaA, Darmstadt, Germany during ECTRIMS 2018," said Luciano Rossetti, Head of Global R&D for the biopharma business of Merck KGaA, Darmstadt, Germany. "As we continue to enhance our understanding of the benefit-risk profile of cladribine tablets and the use of Rebif, we are also excited by the presentation of the first clinical data for a BTK inhibitor (evobrutinib) in an MS patient population."
Additional Merck KGaA, Darmstadt, Germany activities at ECTRIMS 2018:
-- Results of the Merck KGaA, Darmstadt, Germany-sponsored 'MS in the 21st
Century International Unmet Needs Survey' will show that MS patients
have substantially different perceptions of the current unmet needs in
MS compared with healthcare professionals (HCPs).
-- Following on from the #MSInsideOut campaign launch on World MS Day
earlier in the year, Merck KGaA, Darmstadt, Germany will be premiering
the MS Inside Out Documentary film executively produced by Shift.ms
during an event on October 11. At the event, Merck KGaA, Darmstadt,
Germany will shine a light on the untold stories of MS, as well as
revealing the findings and key results from a new global MS carers
survey conducted in collaboration between leading international carer
organizations IACO (International Alliance of Carer Organization) and
Eurocarers. The data presented at ECTRIMS will further demonstrate the
need for a deeper understanding of those affected by MS and their carer.
-- Merck KGaA, Darmstadt, Germany will also be announcing the annual Grant
for Multiple Sclerosis Innovation (GMSI) Award winners in Berlin. First
launched at ECTRIMS 2012, the GMSI Award 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.
-- The company will be holding a press event on Wednesday, 10 October 2018,
15:00-16:25 (CET) at CityCube Conference Center (Room: London 1),
Berlin, Germany.
Below are a selection of abstracts that have been accepted for presentation at ECTRIMS 2018:
Cladribine Tablets Presentations
---
Title
Authors
Abstract No.
Presentation Date/Time/Session
--- ---
An exploratory analysis of Giovannoni G, Rammohan K, Cook S,
the efficacy of Cladribine Soelberg-Sorensen P, Vermersch P,
Tablets 3.5mg/kg in Keller B, Verdun di Cantogno E
patients with relapsing
multiple sclerosis
stratified according to age
above and below 45 years in
the CLARITY study
A-0950-0028-00859
Session Title: Poster Session 3
Session Date: 12.10.2018
Presenting Time: 12:15-14:15 h
--- ---
Sustained efficacy in Vermersch P, Giovannoni G,
relapsing remitting multiple Soelberg-Sorensen P, Keller B,
sclerosis following switch Jack D
to placebo treatment from
Cladribine Tablets in
patients with high disease
activity at baseline
A-0950-0028-00886
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h.
--- ---
CLARITY: An analysis of Schippling S, Sormani M P, De
severity and frequency of Stefano N, Giovannoni G, Galazka
relapses in patients with A, Keller B, Alexandri N
relapsing-remitting
multiple sclerosis treated
with Cladribine Tablets or
placebo
A-0950-0028-01315
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h.
--- ---
Lymphopenia rates in CLARITY/ Cook S, Giovannoni G, Vermersch P,
CLARITY Extension are Soelberg-Sorensen P, Keller B,
unrelated to disease Jack D
activity at baseline
A-0950-0028-00836
Session Title: Poster Session 2
Session Date: 11.10.2018
Presenting Time: 17:15-19:15 h.
--- ---
Updated safety analysis of Cook S, Giovannoni G, Leist T, Syed
Cladribine Tablets in the S, Nolting A, Schick R
treatment of patients with
multiple sclerosis
A-0950-0028-00889
Session Title: Poster Session 2
Session Date: 11.10.2018
Presenting Time: 17:15-19:15 h
--- ---
Durability of NEDA-3 status
in patients with relapsing
multiple sclerosis receiving
Cladribine Tablets: CLARITY
Extension Giovannoni G, Keller B, Jack D
A-0950-0028-01763
Session Title: Poster Session 2
Session Date: 11.10.2018
Presenting Time: 17:15-19:15 h
--- ---
ADA genetic variants Stampanoni Bassi M, Buttari F,
influence central Simonelli I, Sica F, Furlan R,
inflammation and clinical Marfia G A, Salvetti M, Uccelli A,
characteristics in MS: Matarese G, Visconti A, Centonze D
implications for cladribine
treatment
A-0950-0028-01895
Poster Session 1
10 October 2018
Presenting Time: 17:00-19:00 h
--- ---
Neuroblastoma cell line and Ruggieri M, Mastrapasqua M, Gargano
lymphocytes talk for C D, Palazzo C, Frigeri A,
cladribine influenced Paolicelli D, Visconti A, Trojano
apoptosis and inflammation M on behalf of MSRUN group.
pathways in Multiple
Sclerosis (MS): an "in
vitro" study
A-0950-0028-01704
ePoster
--- ---
Dissection of the distinct Carlini F, Ivaldi F, Kerlero de
susceptibility of Rosbo N, Boschert U , Visconti A,
hematopoietic precursors and Uccelli A
immune cells to cladribine
A-0950-0028-01855
ePoster
--- ---
Gene expression profiles of Mechelli R, Manfrè G, Pellicciari
proteins involved in G, Reniè R, Romano C, Ristori G,
Cladribine metabolism and Visconti A, Salvetti M on behalf
their possible correlation of MSRUN group
with Epstein-Barr virus
variants
A-0950-0032-01730
Poster Session 3
12 October 2018
Presenting Time: 12:15-14:15 h
--- ---
A Systematic Review of Real- Edwards NC, Edwards RA, Dellarole
world Adherence and A, Grosso M, Phillips A
Persistence of Daily Oral
Disease-Modifying Drugs
(Dimethyl Fumarate,
Fingolimod, and
Teriflunomide) in Multiple
Sclerosis
TBC
Poster Session 3
12 October 2018
Presenting Time: 12:15-14:15 h
--- ---
Rebif(R) (interferon beta-1a) Presentations
---
Subcutaneous Interferon beta- Harty G, Wong S L, Gillett A,
1a, 10-Year Results from Davies A
the United Kingdom Multiple
Sclerosis Risk Sharing
Scheme
A-0950-0030-00894
Session Title: Poster Session 2
Session Date: 11.10.2018
Presenting Time: 17:15-19:15 h.
--- ---
Rapid reduction of lesion De Stefano N, Giorgio A, Gentile G,
accumulation in specific Stromillo M L, Visconti A,
white matter tracts as Battaglini M
assessed by lesion mapping
in RR-MS patients treated
with IFN beta-1a
A-0950-0023-02002
ePoster
--- ---
Dynamics of pseudo-atrophy De Stefano N, Giorgio A, Gentile G,
in RRMS patients treated Stromillo M L, Visconti A, Sormani
with Interferon beta-1a as M P, Battaglini M
assessed by monthly brain
MRI
A-0950-0023-02027
Session Title: Poster Session 2
Session Date: 11.10.2018
Presenting Time: 17:15-19:15 h.
--- ---
A Real-World Comparison of Hayward B, Cardoso S, Grosso M,
Infections and Lymphocyte Ansari S, Napoli S
Counts among Relapsing-
Remitting Multiple Sclerosis
Patients 50 years or older
treated with Subcutaneous
Interferon-Beta 1a or
Dimethyl Fumarate
A-0950-0031-02072
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h.
--- ---
Value of the MoCA test to K. Charest, A. Tremblay, R.
detect cognitive impairment Langlois, É. Roger, P. Duquette,
in MS patients without I. Rouleau
subjective cognitive
complaints
A-0950-0009-01537
ePoster
--- ---
Rebif(R) (interferon beta-1a) Late-breaker Presentation
---
Pregnancy and Infant Outcomes Hellwig K, Geissbuehler Y, Sabidó
with Interferon Beta: Data M, Popescu C, Adamo A, Klinger J,
from the European Interferon Huppke P, Ornoy A, Korhonen P,
Myhr K-M, Montgomery S , Burkill
S on behalf of the European
Interferon Beta Pregnancy Study
Group
A-0950-0000-02658
Session Title: Poster Session 3
Beta Pregnancy Registry and Population Based Registries in
Finland and Sweden
Session Date: Friday, 12 October 2018
Presenting Time: 12.15 - 14.15 h
--- ---
Evobrutinib (Bruton's Tyrosine Kinase Inhibitor) Presentations
---
Safety, Tolerability, Becker A, Martin E, Ona V, Mitchell
Pharmacokinetics and DY, Willmer J, Johne A
Concentration-QT Analysis
of the Novel BTK Inhibitor
Evobrutinib (M2951) in
Healthy Volunteers
A-0950-0028-01166
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h
--- ---
BTK Inhibition Prevents Alankus YB, Grenningloh R,
Inflammatory Macrophage Haselmeyer P, Bender, A, Bruttger
Differentiation: A Potential J
Role in MS
A-0950-0028-01194
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h.
--- ---
Inhibition of Bruton's Torke S, Grenningloh R, Boschert
Tyrosine Kinase Selectively U, Weber MS
Prevents Antigen-Activation
of B Cells and Ameliorates B
Cell-Mediated Experimental
Autoimmune Encephalomyelitis
A-0950-0028-01220
Session Title: Poster Session 1
Session Date: 10.10.2018
Presenting Time: 17:00-19:00 h.
--- ---
Evobrutinib (Bruton's Tyrosine Kinase Inhibitor) Late-breaker Presentation
---
Primary analysis of a Montalban X, Arnold DL, Weber MS,
randomised, placebo- Staikov I, Piasecka-Stryczynska
controlled, phase 2 study of K, Willmer J, Martin E, Dangond F,
the Bruton's tyrosine kinase Wolinsky JS
inhibitor evobrutinib
(M2951) in patients with
relapsing multiple sclerosis
A-0950-0000-02722
Scientific Session 17: Late Breaking News
Scientific Session, Hall A
Session Date: 12.10.2018
Presenting Time: 14:39-14:51 h
--- ---
Additional Merck KGaA, Darmstadt, Germany-sponsored Presentations
---
Comparing patient and Rieckmann P, Langdon D on behalf of
healthcare professional MS in the 21st Century Steering
perceptions on multiple Group, and Contango E V
sclerosis management and
care - where do their
priorities differ? Results
from a qualitative survey.
A-0950-0034-01926
Session Title: Poster Session 3
Session Date: 12.10.2018
Presenting Time: 12:15-14:15 h.
--- ---
MS in the 21st Century Rieckmann P, Langdon D on behalf of
mapping study identifying MS in the 21st Century Steering
the global educational Group, and Contango E V
offerings for multiple
sclerosis patients
A-0950-0034-01860
ePoster
--- ---
About Cladribine Tablets
Cladribine tablets is an investigational short-course oral therapy that is thought to selectively target lymphocytes which may be integral to the pathological process of relapsing MS (RMS). Cladribine tablets is currently under clinical investigation and not approved for the treatment for any use in the United States. MAVENCLAD(®) has received approvals for patients with highly active RMS as defined by clinical or imaging features in the European Union (EU), Israel, Argentina, United Arab Emirates, Chile and Lebanon. In December 2017, Health Canada and the Therapeutic Goods Administration (TGA) in Australia approved MAVENCLAD(®) for the treatment of relapsing-remitting MS (RRMS).
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
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 follow-up safety registry of
multiple sclerosis patients who participated in cladribine tablets
clinical studies.
The clinical development program of cladribine tablets in MS comprises close to 12,000 patient years of data with over 2,700 patients included in the clinical trial program, and up to 10 years of follow-up in some patients.
In the two-year CLARITY study, the most commonly reported adverse event (AE) in patients treated with cladribine tablets was lymphopenia. 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.
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 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.
Rebif full prescribing information is available at http://www.emdserono.com/ms.country.us/en/images/Rebif_PI_tcm115_140051.pdf?Version=
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 KGaA, Darmstadt, Germany and Multiple Sclerosis
For more than 20 years, Merck KGaA, Darmstadt, Germany has been relentlessly focused on understanding the journey people living with MS face in order to create a meaningful, positive experience for them and the broader MS community. However, there is still much that is unknown about this complex and unpredictable disease. Merck KGaA, Darmstadt, Germany is digging deeper to advance the science and reconstruct a new understanding of MS, inside and out. We are committed to delivering solutions that improve the lives of all those affected by MS.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, is a leading science and technology company in healthcare, life science and performance materials. More than 53,000 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 2017, Merck KGaA, Darmstadt, Germany, generated sales of EUR 15.3 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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