New Data Analyses at ECTRIMS Highlight Benefit-Risk Profile of Investigational Cladribine Tablets in Relapsing Multiple Sclerosis

 

Data suggest Cladribine Tablets may significantly increase proportion of patients exhibiting no evidence of disease activity versus placebo in a post-hoc analysis 

Analysis of 10,000 patient years of safety data provides additional characterization of safety profile

Further data evaluate the relative selectivity of Cladribine Tablets for the adaptive immune system 

 

Darmstadt, Germany, October 26, 2017 – Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced new benefit-risk data for investigational Cladribine Tablets, for the treatment of relapsing multiple sclerosis (MS), at MSParis2017 (7th Joint ECTRIMS-ACTRIMS Meeting) in Paris, France. A post hoc analysis in high disease activity subgroups from the 2-year CLARITY study demonstrated that Cladribine Tablets significantly increased the proportion of patients with no evidence of disease activity (NEDA) compared with placebo (43.7% vs 8.7%)1. This analysis is consistent with results seen in the broader CLARITY patient population. 

Late-breaking safety analysis including patients with up to 8-years follow-up from the monotherapy oral (3.5 mg/kg) cohorts of CLARITY, CLARITY Extension, ORACLE-MS studies and the PREMIERE registry reinforced safety conclusions of the earlier meta-analysis.2

These data presented at MSParis2017 showed:

  • - A detailed safety analysis from CLARITY, CLARITY Extension, ORACLE-MS studies, and the PREMIERE registry was consistent with findings of previous integrated safety analyses regarding Cladribine Tablets’ association with lymphopenia Grade 3 or 4 (severe).3
  • - An analysis of T lymphocyte (T cells) subpopulations from the ORACLE-MS study provide a detailed assessment of the changes that occur in the adaptive immune system following Cladribine Tablets treatment.4
  • - An analysis of neutrophils and monocytes from patients in CLARITY or CLARITY Extension, including time spent in the PREMIERE registry, demonstrated that the effect of Cladribine Tablets treatment on these innate immune cell subsets, compared to patients treated with placebo.5

“These important data provide further detail on how Cladribine Tablets targets the immune system in patients with MS, as well as further insights into its efficacy and safety,” said Dr. Andrew Galazka, Senior Vice President for Scientific Affairs at Merck KGaA, Darmstadt, Germany.

In addition to Cladribine Tablets presentations, Merck KGaA, Darmstadt, Germany, also presented data on its well-established relapsing MS product, Rebif® (interferon beta-1a). A post-hoc analysis of patient data from the PRISMS study investigated the association between the MAGNIMS (Magnetic Resonance Imaging in MS) score at Year 1 and long-term clinical disease activity free (CDAF) status and disability progression. The score, when calculated in Year 1 of treatment with Rebif®, was shown to accurately predict the risk of a CDA (clinical disease activity) event or disability progression in patients with MS.6 Further data on NEDA and real-world evidence will be presented.

For up-to-date information and activities during MSParis2017, follow Merck KGaA, Darmstadt, Germany, on Twitter (@EMDGroup) or #AddressMS.

 

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 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 adult patients with highly active relapsing forms of multiple sclerosis (RMS) as defined by clinical or imaging features 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 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.
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.

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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1Giovannoni G. ECTRIMS ACTRIMS 2017 [Abstract No. P1143] Proportions of Patients with Highly Active RMS Achieving No Evidence of Disease Activity (NEDA) in Response to Cladribine Tablets in CLARITY
2Galazka A. An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis (RMS).
3Cook S. ECTRIMS ACTRIMS 2017 [Abstract No. P1142] Infections During Periods of Grade 3 or 4 Lymphopenia in Patients Taking Cladribine Tablets 3.5 mg/kg: Data from an Integrated Safety Analysis
4Stuve O. Effects of Cladribine Tablets on CD4+ T Cell Subsets in the ORACLE-MS Study: Results from an Analysis of Lymphocyte Surface Markers.
5Soelberg-Sorensen P. ECTRIMS ACTRIMS 2017 [Abstract No. P1141] Innate Immune Cell Counts in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS) Treated With Clabribine Tablets 3.5mg/kg in CLARITY and CLARITY Extension
6Sormani MP. 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.

 

For further information: Alice McGrail +1-781-681-2886