Merck KGaA Submits Application For Cladribine Tablets As Multiple Sclerosis Therapy In Europe

Main Category: Multiple Sclerosis
Also Included In: Regulatory Affairs / Drug Approvals;  Clinical Trials / Drug Trials
Article Date: 25 Jul 2009 - 1:00 PDT

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Merck KGaA announced the submission of a marketing authorization application (MAA) to the European Medicines Agency (EMEA) for Cladribine Tablets, Merck's proprietary investigational oral formulation of cladribine, as a therapy for patients with relapsing-remitting multiple sclerosis (MS). Cladribine Tablets could become the first orally administered disease-modifying therapy available for patients with MS, as all disease-modifying therapies currently approved for the treatment of MS are injectable.

"The submission of Cladribine Tablets to the EMEA brings us closer to the possibility of providing an oral short-course treatment to patients with multiple sclerosis and underscores our commitment to provide new options for the management of relapsing-remitting multiple sclerosis," said Roberto Gradnik, Executive Vice President Commercial Europe of the division Merck Serono. "We look forward to working with the EMEA and the European member states' authorities." The MAA submission is supported by results from the CLARITYa study, a two-year, randomized, double-blind, placebo-controlled Phase III trial of Cladribine Tablets in patients with relapsing-remitting MS. The CLARITY data were presented at the 61st Annual Meeting of the American Academy of Neurology (AAN) in April 2009 and at the 19th Meeting of the European Neurological Society (ENS) in June 2009.

Merck is currently submitting new drug applications for Cladribine Tablets in several other countries, including the United States in the current quarter.

a) CLARITY: CLAdRIbine Tablets Treating MS OrallY

CLARITY study

The CLARITY study was a two-year (96-week), randomized, double-blind, placebo-controlled, international trial. It randomized 1,326 patients with relapsing-remitting MS according to the revised McDonald criteria2. Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of Cladribine Tablets or matching placebo tablets (1:1:1 ratio). Cladribine Tablets were given in two or four treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days, which means study patients took Cladribine Tablets for 8 to 20 days during the year. In the second year, two treatment courses were administered to all patient groups. The primary endpoint of the CLARITY study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints, proportion of subjects qualifying relapse-free and disability progression at 96 weeks. Out of the 1,326 randomized patients, 90% of patients treated with Cladribine Tablets completed the study (92% in the lower total dose group and 89% in the higher total dose group) compared to 87% in the placebo group.

Cladribine Tablets

Merck Serono's proprietary oral formulation of cladribine (Cladribine Tablets) is currently being evaluated in Phase III as a treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS.

The clinical development program for cladribine tablets includes:

-- The CLARITY extension study: a two-year placebo-controlled extension of the CLARITY study, designed to provide data on the long-term safety and efficacy of extended administration of Cladribine Tablets for up to four years

-- The ORACLE MS study: a two-year Phase III placebo-controlled trial 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). This trial was announced in September 2008 and is ongoing.

-- The ONWARD study: a Phase II placebo-controlled trial 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. This trial was announced in January 2007 and is ongoing.

Cladribine Tablets have been granted a fast track designation by the US Food and Drug Administration based on the need for an oral therapy in a subset of patients with relapsing forms of multiple sclerosis.

Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) with Rebif®(interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including 'Cladribine Tablets', currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.

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 more than two 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.

Source: Multiple sclerosis