Merck Serono Announces CHMP Opinion for Cladribine Tablets in MS (1)

GENEVA, September 24, 2010 /PRNewswire/ --

-- Merck Serono is Committed to Making Cladribine Tablets Available to MS Patients in Europe and is Evaluating all Options to Gain Approval in the European Union

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a negative opinion regarding the marketing authorization application (MAA) for Cladribine Tablets as a treatment for relapsing-remitting multiple sclerosis (MS). The CHMP is of the opinion that based on currently available data the benefits of Cladribine Tablets do not outweigh its risks. Merck Serono is committed to making Cladribine Tablets available to MS patients in Europe and is evaluating all options to gain approval in the European Union, including a potential appeal to request re-examination of the submission by the CHMP, in accordance with the current European regulatory legislation.

"We are disappointed by the CHMP opinion, but remain fully committed to the potential of Cladribine Tablets to meet an unmet medical need as an oral, short-course, disease-modifying drug for multiple sclerosis," said Elmar Schnee, President of Merck Serono. "With the considerable support of the multiple sclerosis community and backed by the recent approvals in Australia and Russia, we will continue to work with the CHMP to address the committee's concerns and pursue a way forward to make Cladribine Tablets available to patients from the European Union."

"Multiple sclerosis is a heterogeneous disease and currently available treatments do not meet the medical needs of all patients with active disease," said Professor Gavin Giovannoni, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, United Kingdom, and principal investigator of the CLARITY[1] study. "As a clinician, I hope that a way forward will be found to allow people suffering from this devastating disease to have the option of benefiting from Cladribine Tablets therapy."

Cladribine Tablets were recently approved in Australia and Russia, as a treatment of relapsing-remitting MS, also under the trade name Movectro(R), and are under regulatory review in other countries, including the United States, where the application has been granted Priority Review by the FDA. Cladribine Tablets registration applications are supported by the results from the CLARITY study, the largest placebo-controlled Phase III clinical trial in relapsing-remitting MS completed to date, involving over 1,300 patients with relapsing-remitting multiple sclerosis. Ongoing clinical trials with Cladribine Tablets will continue as planned.

[1] CLARITY: CLAdRIbine Tablets Treating MS OrallY

CLARITY study design

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 criteria. 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 (3.5 mg/kg total dose) or four (5.25 mg/kg total dose) treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days (depending on patient weight), 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, meaning that patients took Cladribine Tablets for 8 to 10 days during the year.

The primary endpoint of the CLARITY study was the relapse rate over 96 weeks. Secondary endpoints included MRI endpoints, proportion of subjects relapse-free and disability progression at 96 weeks.

About Cladribine Tablets

Merck Serono's oral formulation of cladribine (Cladribine Tablets) is an investigational 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. Merck Serono initiated global filings for Cladribine Tablets in mid-2009 and, to date has submitted regulatory applications for Cladribine Tablets covering about 40 countries. Cladribine Tablets was granted its first marketing approval in July 2010, in Russia.

The clinical development program for Cladribine Tablets includes:

-- The CLARITY (CLAdRIbine Tablets treating MS orallY) study and its extension: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients with relapsing-remitting MS and the CLARITY EXTENSION two-year Phase III 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 (ORAl CLadribine in Early 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.

-- The ONWARD (Oral Cladribine added oN to interferon beta-1a in patients With Active Relapsing Disease) 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.

-- The PREMIERE (PRospective observational long-term safEty registry of Multiple sclerosis patIEnts who have participated in CladRibinE clinical trials) registry: an eight-year observational safety registry of patients who have participated in Cladribine Tablets clinical trials, designed to support the evaluation of the long-term safety of Cladribine Tablets in MS.

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 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.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. In the United States and Canada, EMD Serono operates through separately incorporated affiliates.

Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and metabolic disorders (Saizen(R) and Serostim(R), somatropin), (Kuvan(R), sapropterin dihydrochloride) as well as cardiometabolic diseases (Glucophage(R), metformin), (Concor(R), bisoprolol), (Euthyrox(R), levothyroxine). Not all products are available in all markets.

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