Merck Serono Announces Outcome of Its Request for Reexamination of CHMP Opinion for Cladribine Tablets in MS

GENEVA, January 21, 2011 /PRNewswire/ --

    
    - CHMP Confirms its Initial Negative Opinion Regarding the
      Marketing Authorization Application for Cladribine Tablets

    - Merck Serono Remains 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

Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that following its request for reexamination, the Committee for Medicinal Products for Human Use (CHMP) confirmed its previous position and adopted a final negative opinion regarding the marketing authorization application (MAA) for Cladribine Tablets as a treatment for relapsing-remitting multiple sclerosis (MS).

The majority of CHMP members were of the opinion that the benefits of Cladribine Tablets do not outweigh its risks based on data submitted. However, some CHMP members did not share this opinion and voted in favor of a conditional marketing authorization of Cladribine Tablets for the indication discussed during the reexamination procedure.

"We are disappointed by the CHMP opinion however we continue to believe that our data support Cladribine Tablets as a treatment option for patients with relapsing forms of MS," said Dr. Bernhard Kirschbaum, Merck Serono's Head of Research and Development. "We 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 and will evaluate our options for bringing this therapeutic option to patients who could benefit from it also in Europe."

Merck Serono remains committed to completing the ongoing clinical trials with Cladribine Tablets. The Data Safety Monitoring Board that independently oversees the conduct of these trials recently concluded that they should continue. These trials, which are fully enrolled, will provide additional information on the efficacy and safety of Cladribine Tablets in MS. Top-line results from the CLARITY(1) EXTENSION and ORACLE MS(2) studies are expected by the end of 2011. Top-line results from the ONWARD(3) study are expected in the first half of 2012.

Cladribine Tablets are approved and available under the trade name Movectro(R) in Australia and Russia as a treatment of relapsing-remitting MS and are under regulatory review in other countries, including the United States where the application has been granted Priority Review by the Food and Drug Administration (FDA). Cladribine Tablets registration applications are supported by the results from the CLARITY study, involving over 1,300 patients with relapsing-remitting multiple sclerosis.

1 CLARITY: CLAdRIbine Tablets treating MS orallY

2 ORACLE MS: ORAl CLadribine in Early MS

3 ONWARD: Oral Cladribine added oN to interferon beta-1a in patients With Active Relapsing Disease

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. Cladribine Tablets were approved in Russia in July 2010 and in Australia in September 2010 as a treatment of relapsing-remitting MS and are under regulatory review in other countries.

    
    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 biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. In the United States and Canada, EMD Serono operates as a separately incorporated affiliate of Merck Serono.

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.

With an annual R&D expenditure of over EUR 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in rheumatology.

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.7 billion in 2009, a history that began in 1668, and a future shaped by approximately 40,000 employees in 64 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

For more information, please visit http://www.merckserono.com or http://www.merck.de