BIOTECH
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`Merck Receives Complete Response Letter From FDA on
`Cladribine Tablets New Drug Application
`Mar 2, 2011 8:08am
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`Darmstadt, Germany, March 2, 2011 - Merck KGaA announced todaythat it received a complete responseletter from the U.S. Food and
`Drug Administration (FDA) on the new drugapplication (NDA) for Cladribine Tablets, Merck's proprietary investigational oral
`formulation of cladribine, as a therapy for relapsing-remitting multiple sclerosis (MS).
`
`A complete responseletter (CRL) is issued by the FDA whenthe agency's review ofa file is complete and the application cannot be
`approvedin its present form. In the complete responseletter, the FDA concluded that substantial evidence of Cladribine Tablets’
`effectiveness was provided by the CLARITY1 study. However, the FDA has requested the Companyprovide an improved understanding
`ofsafety risks and the overall benefit-risk profile either through additional analyses or by additional studies. Merck intends to request
`an end-of-review meeting with the FDAto clarify next steps and to identify whether data from completed and ongoing clinical studies
`can address the Agency's questions.
`"Our commitmentto transform the way people living with MS approach their therapy options remainssteadfast," said Fereydoun
`Firouz, President and CEOof Merck's U.S. subsidiary EMD Serono,Inc. "We look forward to working with the FDAto 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 ongoingclinical trials with Cladribine Tablets. Thesetrials, which are fully enrolled,will
`provide additional information ontheefficacy and safety of Cladribine Tablets in MS. Top-line results from the CLARITY EXTENSION
`and ORACLE MS2studies are expected by the end of 2011. Top-line results from the ONWARD3 study are expectedin thefirst half of
`2012.
`
`Cladribine Tablets are approved andavailable under the trade name Movectro® in Australia and Russia as a treatmentofrelapsing-
`remitting MS and are underregulatory review in other countries.
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`1 CLARITY: CLAdRIbine Tablets treating MS orallY
`2 ORACLE MS: ORAI CLadribine in Early MS
`3 ONWARD: Oral Cladribine added oNto interferon beta-1a in patients With Active Relapsing Disease
`AboutCladribine 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 thoughtto 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 treatmentof relapsing-remitting MS and are underregulatory review in
`other countries.
`
`Theclinical development program for Cladribine Tablets includes:
`- The CLARITY (CLAdRIbine Tablets treating MS orallY) study and its extension: a two-year PhaseIII placebo-controlled trial designed
`to evaluate the efficacy and safety of Cladribine Tablets as a monotherapyin patients with relapsing-remitting MS and the CLARITY
`EXTENSIONtwo-year PhaseIII study designed to provide data on the long-term safety andefficacy of extended administration of
`Cladribine Tablets for up to four years.
`- The ORACLE MS(ORAICLadribine in Early MS) study: a two-year PhaseIII placebo-controlled trial designed to evaluate the efficacy
`andsafety of Cladribine Tablets as a monotherapyin patients at risk of developing MS(patients who have experienceda first clinical
`event suggestive of MS). This trial was announced in September2008.
`- The ONWARD (Oral Cladribine added oNto 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 treatmentto patients with
`relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was
`announcedin January 2007.
`- The PREMIERE(PRospective observational long-term safEty registry of Multiple sclerosis patIEnts who haveparticipated in
`CladRibinE clinical trials) registry: an eight-year observational safety registry of patients who haveparticipated 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
`symptomscanvary, the most common symptomsof MSinclude blurred vision, numbnessortingling in the limbs and problems with
`strength and coordination. The relapsing forms of MS are the most common.
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`Merck 2037
`Merck 2037
`TWi v Merck
`TWi v Merck
`IPR2023-00050
`IPR2023-00050
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