12/20/23, 11:32 PM
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`Merck Receives Complete Response Letter From FDA on Cladribine Tablets New Drug Application | Fierce Biotech
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`BIOTECH
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`Merck Receives Complete Response Letter From FDA on
`Cladribine Tablets New Drug Application
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`Mar 2, 2011 8:08am
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`Darmstadt, Germany, March 2, 2011 - Merck KGaA announcedtodaythat it received a complete responseletter from the U.S. Food
`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).
`
`Acomplete response letter (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 Company provide an improved understanc
`of safety risks and the overall benefit-risk profile either through additional analyses or by additional studies. Merck intends to requ
`an end-of-review meeting with the FDAto clarify next steps and to identify whether data from completed and ongoingclinical stu
`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 CEO of Merck's U.S. subsidiary EMD Serono,Inc. "We look forward to working with the FDA to address the sa
`issuesin its letter and will continue to move toward identifying a potential path that provides patients and physicians the opportu
`to have access to Cladribine Tablets in the treatment of MS."
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`Merck remains committed to completing the ongoing clinical trials with Cladribine Tablets. Thesetrials, which are fully enrolled,
`provide additional information on theefficacy and safety of Cladribine Tablets in MS. Top-line results from the CLARITY EXTENS]
`and ORACLE MS2studies are expected by the end of 2011. Top-line results from the ONWARD3study are expectedin the first half
`2012.
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`Cladribine Tablets are approved andavailable under the trade name Movectro® in Australia and Russia as a treatmentof relapsing
`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
`About Cladribine Tablets
`
`MerckSerono’soral formulation of cladribine (Cladribine Tablets) is an investigational treatment for patients with relapsing forms
`multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white t
`cells, particularly lymphocytes, which are thoughtto be involved in the pathological process of MS. Cladribine Tablets were approv
`Russia in July 2010 andin Australia in September 2010 as a treatment of relapsing-remitting MS and are underregulatory review i
`other countries.
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`Theclinical development program for Cladribine Tablets includes:
`- The CLARITY (CLAdRIbine Tablets treating MS orallY) study andits extension: a two-year PhaseIII placebo-controlled trial desi
`to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients with relapsing-remitting MS and the CLART]
`EXTENSIONtwo-year PhaseIII 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 (ORAI CLadribine in Early MS) study: a two-year PhaseIII placebo-controlled trial designed to evaluatetheeffic
`and safety of Cladribine Tablets as a monotherapyin patientsat risk of developing MS (patients who have experienceda first clinic
`event suggestive of MS). This trial was announced in September 2008.
`- The ONWARD(Oral Cladribine addedoN to interferon beta-1a in patients With Active Relapsing Disease) study: a PhaseII placel
`controlled trial designed primarily to evaluate the safety andtolerability 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
`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 have participated in Cladribine Tabl
`clinical trials, designed to support the evaluation of the long-term safety of Cladribine Tablets in MS.
`
`About multiple sclerosis
`
`https:/Awww.fiercebiotech.com/biotech/merck-receives-complete-response-letter-from-fda-on-cladribine-tablets-new-drug-application
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`MERCK2038
`HOPEWELL v MERCK
`IPR2023-00480
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`MERCK 2038
`HOPEWELL v MERCK
`IPR2023-00480
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`12/20/23, 11:32 PM
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`Merck Receives Complete Response Letter From FDA on Cladribine Tablets New Drug Application | Fierce Biotech
`
`Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common, non-traumati
`disabling neurological disease in young adults.It is estimated that approximately two million people have MS worldwide. While
`symptomscanvary, the most common symptomsof MSincludeblurred vision, numbnessortingling in the limbs and problemswi
`strength and coordination. The relapsing forms of MS are the most common.
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