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

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

  • CHMP confirms its initial negative opinion regarding the marketing authorization application for Cladribine Tablets
  • Merck 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

Darmstadt, Germany, January 21, 2011 - Merck KGaA 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 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 CLARITY1 EXTENSION and ORACLE MS2 studies are expected by the end of 2011. Top-line results from the ONWARD3 study are expected in the first half of 2012.

Cladribine Tablets are approved and available under the trade name Movectro® in Australia and Russia as a treatment for 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
2ORACLE MS: ORAl CLadribine in Early MS
3ONWARD: 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.

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