Investigational Cladribine Tablets Demonstrates Sustained Disease Control over 4 Years with Maximum of 20 Days Oral Treatment

ROCKLAND, Mass., Sept. 5, 2017 /PRNewswire/ -- EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the US and Canada, today announced the publication of the results of the CLARITY Extension study in the Multiple Sclerosis Journal. The trial, an extension of the Phase III CLARITY study, demonstrated that treatment of patients with relapsing remitting multiple sclerosis (RRMS) with Cladribine Tablets, an investigational short-course oral therapy for two years, followed by two years of treatment with placebo, had clinical benefits similar to those seen with four years of treatment with Cladribine Tablets, with a low risk of severe lymphopenia.

The CLARITY Extension study included 806 patients out of 1,184 patients who completed the CLARITY study. The CLARITY Extension study assessed several clinical efficacy endpoints including annualised relapse rate (ARR) and confirmed 3-month Expanded Disability Status Scale (EDSS) progression. The proportion of patients who remained relapse-free at the end of four years was similar to the patients who received Cladribine Tablets 3.5 mg/kg in CLARITY followed by placebo in CLARITY Extension (75.6%), and those who received Cladribine Tablets 3.5 mg/kg in both studies (81.2%). The proportion of patients who remained free of 3-month EDSS progression was also similar between the treatment groups (72.4% vs 77.4%).

"Today's publication further strengthens the evidence for the use of Cladribine Tablets in MS, demonstrating significant, durable benefits in patients not receiving active treatment after the two short courses," said Prof. Gavin Giovannoni, a lead investigator in the CLARITY studies and Chair of Neurology, Barts and The London School of Medicine and Dentistry. "The data from this publication and other recent articles suggest that Cladribine Tablets selectively targets the adaptive immune system, particularly the b cell compartment, and therefore allows the immune system to reconstitute while still preventing MS disease activity in the majority of treated patients."

The safety outcomes were comparable to those seen in CLARITY; adverse event rates were similar in patients who received Cladribine Tablets in CLARITY followed by placebo in CLARITY Extension, and those who received Cladribine Tablets in both studies. In CLARITY, patients with active relapsing–remitting multiple sclerosis were randomized to placebo or 1 of 2 cumulative doses of Cladribine Tablets (3.5 or 5.25 mg/kg body weight) for 2 years. In CLARITY Extension, patients were administered placebo or a cumulative dose of Cladribine Tablets 3.5 mg/kg body weight. In patients who received Cladribine Tablets 3.5 mg/kg in CLARITY and placebo in CLARITY Extension, the majority of those who experienced Grade ≥ 3 lymphopenia recovered to Grade 0-1 by the completion of CLARITY Extension. Most AEs were classified as mild or moderate. In the patient group receiving placebo in CLARITY Extension following Cladribine Tablets 3.5 mg/kg in CLARITY, 3.1% of patients discontinued because of AEs. The most frequent AE in patients receiving Cladribine Tablets in the CLARITY Extension study was lymphopenia. The majority of lymphopenia events were classified as mild or moderate, and the majority of patients who experienced lymphopenia Grade ≥3 actually experienced Grade 3 only. In CLARITY Extension, herpes zoster infections were most frequent in patients receiving the highest cumulative dose of Cladribine Tablets (4.8%), however the incidence of herpes zoster in all other treatment groups was similar irrespective of cumulative dose (1.1–2.0%).

"Today's data add to the growing evidence for the use of Cladribine Tablets in patients with relapsing MS," said Luciano Rossetti, Head of Global R&D for the biopharma business of EMD Serono. "At EMD Serono we are very excited about the difference Cladribine Tablets could make in the lives of patients with this debilitating condition."

In August, the European Commission (EC) granted Marketing Authorization of the investigational therapy, Cladribine Tablets, marketed as MAVENCLAD^® in the EU, for the treatment of adults with highly active relapsing MS.* Merck KGaA, Darmstadt, Germany plans additional filings for regulatory approval in other countries, including the United States.

* Defined as: patients with 1 relapse during the previous year and ≥ 1 T1 Gd+ lesion or ≥ 9 T2 lesions while on therapy with other DMDs; OR patients with ≥ 2 or more relapses in the previous year, whether on DMD treatment or not.

CLARITY Extension Study Design
The CLARITY Extension study involved 806 patients out of 1,184 patients from the CLARITY study, allowing assessment of the effects of 2 years' additional treatment with Cladribine Tablets beyond the 2-year CLARITY regimen. Patients who received Cladribine Tablets 3.5 mg/kg or 5.25 mg/kg in the CLARITY study were randomised to receive either Cladribine Tablets 3.5 mg/kg or placebo in CLARITY Extension, and patients who received placebo in the original CLARITY study received Cladribine Tablets 3.5 mg/kg in CLARITY Extension.

About Cladribine Tablets
Cladribine Tablets is an investigational short-course oral therapy that selectively and periodically targets 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 the treatment 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 relapsing forms of multiple sclerosis (RMS) 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 four-year Phase III placebo-controlled study following on from 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 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 EMD Serono, Inc.
EMD Serono is the North America biopharma business of Merck KGaA, Darmstadt, Germany - a leading science and technology company - focused exclusively on specialty care. For more than 40 years, the business has integrated cutting-edge science, innovative products and industry-leading patient support and access programs. EMD Serono has deep expertise in neurology, fertility and endocrinology, as well as a robust pipeline of potential therapies in oncology, immuno-oncology and immunology as R&D focus areas. Today, the business has more than 1,100 employees around the country with commercial, clinical and research operations based in the company's home state of Massachusetts.

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