Merck Serono Receives Complete Response Letter From FDA on Cladribine Tablets New Drug Application

GENEVA, March 2, 2011 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that it received a complete response letter (CRL) from the U.S. Food and Drug Administration (FDA) on the new drug application (NDA) for Cladribine Tablets, Merck Serono's proprietary investigational oral formulation of cladribine, as a therapy for relapsing-remitting multiple sclerosis (MS).

A complete response letter is issued by the FDA when the Agency's review of a file is complete and the application cannot be approved in its present form. In the complete response letter, the FDA concluded that substantial evidence of Cladribine Tablets' effectiveness was provided by the CLARITY1 study. However, the FDA has requested the Company provide an improved understanding of safety risks and the overall benefit-risk profile either through additional analyses or by additional studies. Merck Serono intends to request an end-of-review meeting with the FDA to clarify next steps and to identify whether data from completed and ongoing clinical studies can address the Agency's questions.

"Our commitment to transform the way people living with MS approach their therapy options remains steadfast," said Fereydoun Firouz, President and CEO of EMD Serono, Inc. "We look forward to working with the FDA to address the safety issues in its letter and will continue to move toward identifying a path that provides patients and physicians the opportunity to have access to Cladribine Tablets in the treatment of MS."

Merck Serono remains committed to completing the ongoing clinical trials with Cladribine Tablets. 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 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(R) in Australia and Russia as a treatment of relapsing-remitting MS and are under regulatory review in other countries.

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

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), (Egrifta(TM), tesamorelin), 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 9.3 billion in 2010, a history that began in 1668, and a future shaped by more than 40,000 employees in 67 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