Darmstadt, Germany, March 2, 2011 - Merck KGaA announced today that it received a complete response letter from the U.S. Food and
`Drug Administration (FDA) on the new drug application (NDA) for Cladribine Tablets, Merck's proprietary investigational oral
`formulation of cladribine, as a therapy for relapsing-remitting multiple sclerosis (MS).
`
`A complete response letter (CRL) is issued by the FDA when the agency's review of a (cid:232)le 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 bene(cid:232)t-risk pro(cid:232)le either through additional analyses or by additional studies. Merck 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 Merck's U.S. subsidiary 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 potential path that provides patients and physicians the opportunity
`to have access to Cladribine Tablets in the treatment of MS."
`
`Merck remains committed to completing the ongoing clinical trials with Cladribine Tablets. These trials, which are fully enrolled, will
`provide additional information on the ef(cid:232)cacy 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 (cid:232)rst half of
`2012.
`
`Cladribine Tablets are approved and available under the trade name Movectro® 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 ef(cid:232)cacy 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 ef(cid:232)cacy 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 ef(cid:232)cacy
`and safety of Cladribine Tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a (cid:232)rst 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, in(cid:233)ammatory 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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