MILAN, Italy and GENEVA, Switzerland, June 22 /PRNewswire/ --

Merck Serono, a division of Merck KGaA, Darmstadt, Germany,announced today new data from post-hoc analyses of the 2-year (96-week)placebo-controlled CLARITYa Phase III trial using Cladribine Tablets (MerckSerono's proprietary investigational oral formulation of cladribine) to treatpatients with relapsing-remitting multiple sclerosis. These data show thatshort-course oral treatment with Cladribine Tablets resulted in rapid andsustained improvements in clinical and magnetic resonance imaging (MRI)outcomes, which were accompanied by rapid and sustained effects on blood-cellsubtypes implicated in the pathogenesis of multiple sclerosis. The data willbe presented at the 19th Meeting of the European Neurological Society (ENS)in Milan, Italy.(1,2,3,4)

"The early impact on relapse reduction, together with theevidence for sustained benefits over 96 weeks as shown in the CLARITY study,support the short-course annual dosing regimen for Cladribine Tablets," saidProf. Giancarlo Comi, Professor of Neurology at the University Vita-SaluteSan Raffaele in Milan, Italy and an investigator for the CLARITY study."Short-course oral treatment with Cladribine Tablets has the potential tomake a meaningful difference in the lives of people with multiple sclerosisand their families."

A total of 1,326 patients were randomized to one of threedifferent arms of the CLARITY study, consisting of two different doseregimens of Cladribine Tablets or matching placebo tablets (1:1:1 ratio).Cladribine Tablets were given in two (low-dose regimen) or four (high-doseregimen) treatment courses in the first year, with each course consisting ofonce daily administration for four to five consecutive days (depending onpatient weight), which means study patients took Cladribine Tablets for 8 to20 days during the year. In the second year, two treatment courses wereadministered to all patient groups, meaning that patients took CladribineTablets for 8 to 10 days during the year.

In the CLARITY study, Cladribine Tablets significantly reducedthe annualized relapse rate compared with placebo (primary endpoint). Thiseffect was significant (as indicated by non-overlap of 95% confidenceintervals versus placebo) as early as 12 weeks after initiation of treatmentfor patients treated with the low-dose regimen of Cladribine Tablets(low-dose regimen: 0.20; placebo: 0.49), and 16 weeks after initiation oftreatment for both Cladribine Tablets treatment groups (low-dose regimen:0.19; high-dose regimen: 0.21; placebo: 0.44). Effects were sustained throughto the 96 weeks of the study with relative reductions in annualized relapserates greater than 50% for patients treated with Cladribine Tablets withrespect to placebo (low-dose regimen: 0.14; high-dose regimen: 0.15; placebo:0.33 , p<0.001 for both treatment groups).

Lower mean numbers of different types of brain lesions (asmeasured by pre-specified key MRI endpoints) were observed for bothCladribine Tablets treatment groups by the first assessment point (24 weeks)and were sustained through the 96-week evaluation period, achieving highlevels of statistical significance (all p<0.001). The pre-specified key MRIsecondary endpoints were T1 gadolinium-enhanced, active T2 lesions andcombined unique lesions.

The effects of Cladribine Tablets on clinical and MRI measureswere accompanied by rapid and sustained effects on blood-cell subtypesimplicated in the pathogenesis of multiple sclerosis, such as T cells (CD3+,CD4+ and CD8+), and more transiently B cells (CD19+).

Overall, the frequencies of adverse events by MedDRA SystemOrgan Class in both Cladribine Tablets treatment groups from the CLARITYstudy were comparable to those observed in the placebo group. The mostcommonly reported adverse events were headaches, upper respiratory tractinfection, nasopharyngitis and nausea. Lymphopenia, an expected event basedon the presumed mechanism of action of cladribine, occurred more frequentlyin the Cladribine Tablets treatment groups (low-dose regimen: 21.6%;high-dose regimen: 31.5%; placebo: 1.8%). The overall rate and incidence ofinfections in patients treated with Cladribine Tablets and placebo weresimilar. Herpes zoster infections were reported in 2.3% of patients treatedwith Cladribine Tablets. These herpes infections were localized to the skinand responded appropriately to treatment.

Merck Serono plans to submit Cladribine Tablets forregistration to the European Medicines Agency (EMEA) and to the US Food andDrug Administration (FDA) during summer 2009.

a CLARITY: CLAdRIbine Tablets Treating MS OrallY

About the CLARITY study

The CLARITY study was a two-year (96-week), randomized, double-blind,placebo-controlled, international trial. It randomized 1,326 patients withrelapsing-remitting MS according to the revised McDonald criteria(2). Studyparticipants were randomized to one of three different treatment groupsconsisting of two different dose regimens of Cladribine Tablets or matchingplacebo tablets (1:1:1 ratio). Cladribine Tablets were given in two or fourtreatment courses in the first year, with each course consisting of oncedaily administration for four to five consecutive days, which means studypatients took Cladribine Tablets for 8 to 20 days during the year. In thesecond year, two treatment courses were administered to all patient groups.The primary endpoint of the CLARITY study was the qualifying relapse rate at96 weeks. Secondary endpoints included MRI endpoints, proportion of subjectsqualifying relapse-free and disability progression at 96 weeks. Out of the1,326 randomized patients, 90% of patients treated with Cladribine Tabletscompleted the study (92% in the lower total dose group and 89% in the highertotal dose group) compared to 87% in the placebo group.

About Cladribine Tablets

Merck Serono's proprietary oral formulation of cladribine(Cladribine Tablets) is currently being evaluated in Phase III as a treatmentfor patients with relapsing forms of multiple sclerosis (MS). Cladribine is asmall molecule that may interfere with the behavior and the proliferation ofcertain white blood cells, particularly lymphocytes, which are thought to beinvolved in the pathological process of MS.

The clinical development program for cladribine tabletsincludes:

- The CLARITY extension study: a two-year placebo-controlled extension of the CLARITY 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 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 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 and is ongoing.

Cladribine Tablets have been granted a fast track designationby the US Food and Drug Administration based on the need for an oral therapyin a subset of patients with relapsing forms of multiple sclerosis.

About Merck Serono and multiple sclerosis

Merck Serono is a leader in multiple sclerosis (MS) withRebif(R) (interferon beta-1a), a disease-modifying drug used to treatrelapsing forms of MS, which is registered in more than 80 countriesworldwide. Full prescribing information for this product can be obtained bycontacting the Company or visiting its website. Additional therapeuticoptions are currently under development at Merck Serono, including'Cladribine Tablets', currently in Phase III and potentially the first oraltherapy for MS, as well as several products in early stage development. MerckSerono also is taking a leading role in developing an understanding of therole of genetics in MS.

About multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory conditionof the central nervous system and is the most common, non-traumatic,disabling neurological disease in young adults. It is estimated that morethan two million people have MS worldwide. While symptoms can vary, the mostcommon symptoms of MS include blurred vision, numbness or tingling in thelimbs and problems with strength and coordination. The relapsing forms of MSare the most common.

About Merck Serono

Merck Serono is the division for innovative prescriptionpharmaceuticals of Merck, a global pharmaceutical and chemical group.Headquartered in Geneva, Switzerland, Merck Serono discovers, develops,manufactures and markets innovative small molecules and biopharmaceuticals tohelp patients with unmet medical needs. Its North American business operatesin the United States and Canada as EMD 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 alpha), endocrine and metabolic disorders (Saizen(R)and Serostim(R), somatropin), (Kuvan(R), sapropterin dihydrochloride) as wellas cardiometabolic diseases (Glucophage(R), metformin), (Concor(R),bisoprolol), (Euthyrox(R), levothyroxine). Not all products are available inall markets.

With an annual R&D expenditure of around EUR 1bn, Merck Seronois committed to growing its business in specialist-focused therapeutic areasincluding neurodegenerative diseases, oncology, fertility and endocrinology,as well as new areas potentially arising out of research and development inautoimmune and inflammatory diseases.

For more information, please visit http://www.merckserono.com orhttp://www.merck.de

About Merck

Merck is a global pharmaceutical and chemical company withtotal revenues of EUR 7.6 billion in 2008, a history that began in 1668, anda future shaped by 32,700 employees in 60 countries. Its success ischaracterized by innovations from entrepreneurial employees. Merck'soperating activities come under the umbrella of Merck KGaA, in which theMerck family holds an approximately 70% interest and free shareholders ownthe remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. wasexpropriated and has been an independent company ever since.

For more information, please visit http://www.merckserono.com orhttp://www.merck.

References:

(1) G. Giovannoni et al. Clinical efficacy of cladribine tablettherapy in patients with relapsing-remitting multiple sclerosis: results fromthe CLARITY study, a 96-week, Phase III, double-blind, placebo-controlledtrial

(2) P. Soelberg-S?rensen et al. Haematological profiles inpatients treated with cladribine tablets for relapsing-remitting multiplesclerosis: results from the CLARITY study, a 96-week, Phase III,double-blind, placebo-controlled trial

(3) G. Comi et al. Magnetic resonance imaging (MRI) outcomes inpatients with relapsing-remitting multiple sclerosis treated with cladribinetablets: results from the CLARITY study, a 96-week, Phase III, double-blind,placebo-controlled trial

(4) P. Vermersch et al. Rapid and sustained efficacy withcladribine tablet treatment in relapsing-remitting multiple sclerosis:results from the CLARITY study, a 96-week, Phase III, double-blind,placebo-controlled trial

Merck Serono : 9 Chemin des Mines, 1202 Geneva, Switzerland, Media Relations : Tel.: +41-22-414-36-00