EMD Serono to Present New Data on Mavenclad®, Rebif® and the Investigational Therapy Evobrutinib at the AAN Annual Meeting 2019
ROCKLAND, Mass., April 30, 2019 /PRNewswire/ -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced that data from across its multiple sclerosis (MS) portfolio will be presented at the American Academy of Neurology (AAN) 2019 Annual Meeting, May 4-10, 2019 in Philadelphia, PA. The company will present a total of 20 abstracts (18 posters and two platform presentations), including data on MAVENCLAD(®) (cladribine) tablets, the investigational therapy evobrutinib (an oral, selective Bruton's Tyrosine Kinase (BTK) inhibitor) and Rebif(®) (interferon beta-1a).
"The wealth of data to be presented at AAN 2019 highlights our continued progress across our portfolio of marketed products and investigational agents in multiple sclerosis," said Luciano Rossetti, Head of Global Research & Development at EMD Serono. "We are very proud of our commitment to further the understanding of multiple sclerosis and enhance our clinical development program to meet the needs of patients."
Key MAVENCLAD(® )data will include:
-- Post-hoc analysis of the CLARITY Extension study to examine the
durability of no evidence of disease activity-3 (NEDA-3) in relapsing MS
(RMS) patients receiving cladribine tablets
-- Integrated analysis of pooled long-term safety data of cladribine
tablets in patients with MS collated from the CLARITY, CLARITY
Extension, ORACLE-MS studies and the PREMIERE registry
-- A new analysis of the speed of onset of the MRI effect is presented. At
3 months the effect on new inflammatory lesions was apparent in the
ORACLE-MS study. In the same study consistency in clinical outcomes was
observed across different patient subgroups defined by patient and
disease characteristics at baseline
-- Abstracts from the ORACLE-MS study describe the effect of cladribine
tablets on early MS
-- Results from studies investigating the biological effects of cladribine
tablets, including the effect on lymphocyte proliferation, and
endothelial responsiveness to tumor necrosis factor and its effect on
hematopoietic precursors and immune cells, to offer further insights on
the potential mode of action of cladribine tablets
Key evobrutinib data will include:
-- Results of analysis of the efficacy and safety of evobrutinib in
patients with RMS over 48 Weeks: a randomized, placebo-controlled, phase
2 study
Key Rebif(® )data will include:
-- Investigation from the European Interferon Beta (IFN ) pregnancy
registry and Nordic health study into the prevalence of pregnancy
outcomes in IFN -exposed women
-- Results from the IMPROVE study on the dynamics of pseudo-atrophy in RMS
patients treated with interferon beta-1a as assessed by monthly brain
MRI
EMD Serono will also be announcing the launch of a new, collaborative MS research network called 'MS-LINK' (Leadership and Innovation Network), an initiative that brings together a community of multiple sclerosis stakeholders to form a scientific foundation for sustainable transformation of MS care, with the shared goal of improving patient outcomes.
Below is a selection of abstracts that have been accepted for presentation at AAN 2019:
MAVENCLAD (cladribine tablets) data
---
Title
Lead Author
Poster Presentation /Session
--- ---
Durability of NEDA-3 status in
patients with relapsing
multiple sclerosis receiving
cladribine tablets: CLARITY
Extension
Giovannoni G
P3.2-100 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
Cladribine tablets were
associated with rapid onset of
improvements in MRI outcomes
in the ORACLE-MS trial
Scarberry S
P3.2-061 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
The effect of cladribine
tablets on delaying the time
to conversion to CDMS or
McDonald MS is consistent
across subgroups in the
ORACLE-MS study
Bowen J
P3.2-101 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
Untreated Patients with
Multiple Sclerosis: Prevalence
and Characteristics in Denmark
and in the United States
Nørgaard M
P4.2-060 11:30 -18:30 ET, Wednesday 8 May
P4: MS Epidemiology, Co-Morbidities,
and Modifiable Risk Factors
--- ---
Updated safety analysis of
cladribine tablets in the
treatment of patients with
multiple sclerosis
Cook S
P4.2-046 11:30 -18:30 ET, Wednesday 8 May
P4: MS Therapeutics: MOA and Safety
--- ---
Gaps in treatment and treatment
discontinuation among patients
with multiple sclerosis newly-
initiating once- or twice-
daily oral disease-modifying
drugs
Nicholas J
P3.2-102 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
Lymphopenia rates in CLARITY/
CLARITY Extension are
consistent in patients with or
without high disease activity
at baseline
Cook S
P3.2-062 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
Meta-analysis of real-world
adherence and persistence of
maintenance once- or twice-
daily oral disease-modifying
drugs (dimethyl fumarate,
fingolimod, and teriflunomide)
in multiple sclerosis
Nicholas J
P3.2-041 11:30 -18:30 ET, Tuesday 7 May
P3: MS Clinical Trials and
Therapeutic Research
--- ---
ADA genetic variants influence
central inflammation and
clinical characteristics in
MS: implications for
cladribine treatment
Stampanoni
P4.2-044 11:30 -18:30 ET, Wednesday 8 May
Bassi M P4: MS Therapeutics: MOA and Safety
--- ---
Dissection of the distinct
susceptibility of
hematopoietic precursors and
immune cells to cladribine
Carlini F
P4.2-045 11:30 -18:30 ET, Wednesday 8 May
P4: MS Therapeutics: MOA and Safety
--- ---
Neuroblastoma cell line and
lymphocytes talk for
cladribine influenced
apoptosis and inflammation
pathways in Multiple Sclerosis
(MS): an "in vitro" study
Ruggieri M
P2.2-095 11:30 -18:30 ET, Monday 6 May
P2: MS Immunology and Basic Science
--- ---
Gene expression profiles of
proteins involved in
cladribine metabolism and
their possible correlation
with Epstein-Barr virus
variants
Mechelli R
P2.2-096 11:30 -18:30 ET, Monday 6 May
P2: MS Immunology and Basic Science
--- ---
Evobrutinib data
---
Efficacy and Safety of the
Bruton's Tyrosine Kinase
Inhibitor Evobrutinib (M2951)
in Patients with Relapsing
Multiple Sclerosis over 48
Weeks: a Randomized, Placebo-
Controlled, Phase 2 Study
Montalban X
Oral presentation
13:33 ET, Friday 10 May
S56: MS Trials and Treatment
--- ---
Inhibition of Bruton's Tyrosine
Kinase Prevents Inflammatory
Macrophage Differentiation: A
Potential Role in Multiple
Sclerosis
Alankus YB
P2.2-077 11:30 -18:30 ET, Monday 6 May
P2: MS Immunology and Basic Science
--- ---
Inhibition of Bruton's Tyrosine
Kinase Selectively Prevents
Antigen-Activation of B cells
and Ameliorates B-Cell-
Mediated Experimental
Autoimmune Encephalomyelitis
Torke S
P2.2-063 11:30 -18:30 ET, Monday 6 May
P2: MS Immunology and Basic Science
--- ---
Rebif(R) (interferon beta-1a)
---
Pregnancy and Infant Outcomes
with Interferon Beta: Data
from the European Interferon
Beta Pregnancy Registry and MS
Preg study conducted in
Finland and Sweden
Hellwig K 450
13:44 ET, Thursday 9 May
S49: MS Epidemiology and Risk
Stratification
--- ---
Dynamics of Pseudo-Atrophy in
RRMS Patients Treated with
Interferon beta-1a as
Assessed by Monthly Brain MRI
De Stefano N
P5.2-047 11:30 -18:30 ET, Thursday 9 May
P5: MS Neuroimaging
--- ---
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About MAVENCLAD(®)
MAVENCLAD, approved by the U.S. Food and Drug Administration (FDA) on March 29, 2019, is the first and only short-course oral therapy for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS). Patients should follow healthcare provider instructions including cancer screening, contraception and blood tests. The approved dose of MAVENCLAD is 3.5 mg per kg body weight over two years, administered as one treatment course of 1.75 mg per kg per year, each consisting of two treatment weeks. The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes. MAVENCLAD causes a dose-dependent reduction in lymphocyte counts followed by recovery.
Because cladribine is cytotoxic, special handling and disposal instructions should be followed.
MAVENCLAD has been approved in over 50 countries, including the European Union (EU), Canada, Australia and Switzerland, for various relapsing MS indications. Visit www.MAVENCLAD.com for more information.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: MALIGNANCIES and RISK OF TERATOGENICITY
-- Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD
is contraindicated in patients with current malignancy; evaluate the
benefits and risks of the use of MAVENCLAD on an individual patient
basis for patients with prior or increased risk of malignancy.
-- MAVENCLAD is contraindicated for use in pregnant women and in women and
men of reproductive potential who do not plan to use effective
contraception because of the potential for fetal harm.
CONTRAINDICATIONS
-- current malignancy.
-- pregnancy, and women and men of reproductive potential who do not plan
to use effective contraception during MAVENCLAD dosing and for 6 m after
the last dose in each treatment course.
-- human immunodeficiency virus (HIV).
-- active chronic infections (e.g., hepatitis or tuberculosis).
-- history of hypersensitivity to cladribine.
-- breastfeeding while taking MAVENCLAD and for 10 days after the last
dose.
DOSING CONSIDERATIONS: After the completion of 2 treatment courses, do not administer additional MAVENCLAD during the next 2 years. The risk of malignancy with reinitiating MAVENCLAD more than 2 years after completion of 2 treatment courses has not been studied.
ADDITIONAL WARNINGS AND PRECAUTIONS
-- Lymphopenia: In clinical studies, 87% of MAVENCLAD-treated patients
experienced lymphopenia. Concomitant use of MAVENCLAD with hematotoxic
drugs may increase the risk of adverse reactions because of the additive
hematological effects. Monitor lymphocyte counts before and during
treatment, periodically thereafter, and when clinically indicated.
-- Infections: Infections occurred in 49% of MAVENCLAD-treated patients
compared to 44% of patients treated with placebo in clinical studies.
The most frequent serious infections included herpes zoster and
pyelonephritis. Single fatal cases of tuberculosis and fulminant
hepatitis B were reported in the clinical program. Administer
live-attenuated or live vaccines at least 4 to 6 weeks prior to starting
MAVENCLAD. Screen patients for latent infections; consider delaying
treatment until infection is fully controlled. Vaccinate patients
antibody-negative to varicella zoster virus prior to treatment. Monitor
for infections.
-- Hematologic Toxicity: Mild to moderate decreases in neutrophil counts,
hemoglobin levels, and platelet counts were observed. Severe decreases
in neutrophil counts were observed in 3.6% of MAVENCLAD-treated
patients, compared to 2.8% of placebo patients. Obtain complete blood
count (CBC) with differential including lymphocyte count before and
during treatment, periodically thereafter, and when clinically
indicated.
-- Risk of Graft-versus-Host Disease With Blood Transfusions: Irradiation
of cellular blood components is recommended.
-- Liver Injury: Obtain liver function tests prior to treatment.
Discontinue MAVENCLAD if significant injury is suspected.
-- Hypersensitivity: In clinical studies, 11% of MAVENCLAD-treated patients
had hypersensitivity reactions, compared to 7% of placebo patients.
Serious hypersensitivity reactions occurred in 0.5% of MAVENCLAD-treated
patients, compared to 0.1% of placebo patients. If a hypersensitivity
reaction is suspected, discontinue treatment. Do not use MAVENCLAD in
patients with a history of hypersensitivity to cladribine.
Adverse Reactions: The most common adverse reactions with an incidence of >20% for MAVENCLAD are upper respiratory tract infection, headache, and lymphopenia.
Drug Interactions/Concomitant Medication: Concomitant use of MAVENCLAD with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Avoid concomitant use of certain antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD.
Please see the full Prescribing Information, including boxed WARNING for additional information.
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 specific 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.
EMD Serono, Inc. and Multiple Sclerosis
For more than 20 years, EMD Serono 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. EMD Serono is digging deeper to advance the science.
About EMD Serono, Inc.
EMD Serono - the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada - is engaged in the discovery, research and development of medicines for patients with difficult to treat diseases. The business is committed to transforming lives by developing and delivering meaningful solutions that help address the therapeutic and support needs of individual patients. Building on a proven legacy and deep expertise in neurology, fertility and endocrinology, EMD Serono is developing potential new oncology and immuno-oncology medicines while continuing to explore potential therapeutic options for diseases such as psoriasis, lupus and MS. Today, the business has approximately 1,300 employees around the country with commercial, clinical and research operations based in the company's home state of Massachusetts. www.emdserono.com
Contact:
Alice McGrail: +1 781 738 8791
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