New Data Supporting Cladribine Tablets as a Potential New Therapeutic Option Presented at the 62nd AAN Annual Meeting

TORONTO & ROCKLAND, Mass.--(BUSINESS WIRE)--Apr 16, 2010 - EMD Serono, a division of Merck KGaA, Darmstadt, Germany, today announced that new data providing further understanding on Cladribine Tablets as a potential new therapeutic option for relapsing forms of multiple sclerosis (MS) were presented at the 62nd Annual Meeting of the American Academy of Neurology (AAN). Cladribine Tablets, EMD Serono's proprietary investigational oral formulation of cladribine, is currently under regulatory review in a number of countries.

“The relevance of the CLARITY study is further substantiated by the series of additional analyses presented at AAN,” said Bernhard Kirschbaum, Head of Global Research and Development, Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “We are committed to continuing to work with regulatory authorities to bring Cladribine Tablets to patients at the earliest point in time."

The data presented at AAN are from pre-specified and post-hoc analyses of the Phase III CLARITY a clinical trial and show that the administration of Cladribine Tablets in study subjects resulted in:

 

  • Increase in the proportion of patients with disease activity-free status compared with the placebo group over the entire 96-week study (43% and 44% of patients treated with Cladribine Tablets total dose of 3.5 mg/kg and 5.25 mg/kg respectively compared with 16% of patients who received placebo - p<0.001 for both Cladribine Tablets groups) with statistically significant findings as early as 24 weeks (67% and 70% of patients treated with Cladribine Tablets total dose of 3.5 mg/kg and 5.25 mg/kg respectively compared with 39% of patients who received placebo – p<0.001 for both Cladribine Tablets groups). Disease activity-free status was defined as having no clinical activity (no relapse and no sustained disability progression) and no radiological activity (no T1 Gd+ lesions and no active T2 lesions) over the 96-week study 1.
  • Reductions in annualized relapse rate (ARR) compared to the placebo group over 96 weeks across the spectrum of baseline demographics and disease characteristics included in the CLARITY study (gender, age, treatment history, disease history, baseline disease disability, MRI activity and burden of disease) 2
  • Reduced consumption of healthcare resources, a decreased need for societal support, improvements in patient productivity, and reductions in total non-drug expenditure, relative to placebo, as measured by data collected in the CLARITY study with a ˜resource utilization form' at baseline and at scheduled patient visits 3.
  • Decrease of proportions of circulating CD4+ T cells relative to the total number of lymphocytes at the end of treatment periods compared to baseline, while the proportions of other lymphocyte subtypes (CD8+ T, B and natural killer cells) were preserved or increased relative to total lymphocytes. 4

Overall, the frequencies of adverse events by MedDRA System Organ Class in both Cladribine Tablets treatment groups from the CLARITY study were comparable to those observed in the placebo group. The most commonly reported adverse events were headaches, upper respiratory tract infection, nasopharyngitis and nausea. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the Cladribine Tablets treatment groups (3.5 mg/kg total dose: 21.6%; 5.25 mg/kg total dose: 31.5%; placebo: 1.8%). The overall rate and incidence of infections in patients treated with Cladribine Tablets and placebo were similar. Herpes zoster infections were reported in 2.3% of patients treated with Cladribine Tablets. These herpes infections were localized to the skin and responded appropriately to treatment.

CLARITY: CLAdRIbine Tablets Treating MS OrallY

References:

1 Analysis of Clinical and Radiological Disease Activity-Free Status in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Treated with Cladribine Tablets, in the Double-Blind, 96-Week CLARITY Study (presentation S21.008, Wednesday, April 14, 2010, 3:45 pm EDT)

2 Consistent Efficacy of Cladribine Tablets across Multiple Sclerosis and Patient Characteristics, in the Double-Blind, 96-Week CLARITY Study (poster P02.186, Tuesday, April 13, 2010, 3:00 pm-7:30 pm EDT)

Reductions in the annualized relapse rate (ARR) across the various patient strata:

 

  • Gender (man or woman): Relative reductions in ARR were 61% and 55%, respectively, for 3.5 mg/kg and 68% and 48%, respectively, for 5.25 mg/kg (all p<0.001 versus placebo)
  • Age (‰¤40 or >40): Relative reductions in ARR were 58% and 57%, respectively, for 3.5 mg/kg and 63% and 46%, respectively, for 5.25 mg/kg (all p<0.001 versus placebo)
  • Treatment history (previously treated with disease-modifying therapy or drug-naïve patients): Relative reductions in ARR were 45% and 61%, respectively, for 3.5 mg/kg and 58% and 58%, respectively for 5.25 mg/kg (all p‰¤0.0013 versus placebo)
  • Number of relapses in the 12 months preceding study entry (‰¤1, 2 or ‰¥3 relapses): Relative reductions in ARR ranged from 48% (relative risk: 0.50; 95% confidence interval: 0.37, 0.66) to 76% (relative risk: 0.24; 95% confidence interval: 0.09, 0.64) depending on dose group (all p‰¤0.006 versus placebo)
  • Level of disability at baseline (EDSS 0-2.5 or EDSS ‰¥3): Relative reductions in ARR ranged from 49% (relative risk: 0.51; 95% confidence interval: 0.38, 0.68) to 65% (relative risk: 0.35; 95% confidence interval: 0.25, 0.50) depending on dose group (all p<0.001 versus placebo)
  • T1 Gd+ lesions (no lesions or ‰¥1 lesion): Relative reductions in ARR ranged from 45% (relative risk: 0.55; 95% confidence interval: 0.42, 0.72) to 75% (relative risk: 0.26; 95% confidence interval: 0.17, 0.40) depending on dose group (all p<0.001 versus placebo)
  • T2 lesion volume (>or ‰¤ median T2 lesion volume status): Relative reductions in ARR ranged from 48% (relative risk: 0.53; 95% confidence interval: 0.39, 0.71) to 67% (relative risk: 0.33; 95% confidence interval: 0.24, 0.47) depending on dose group (all p<0.001 versus placebo)

3 Health Resource Utilization in the CLARITY Study (poster P01.205, Tuesday, April 13, 2010, 7:30 am-12:00 pm EDT)

4 Effects of Cladribine Tablets on Circulating Lymphocyte Subsets in the 96-Week CLARITY Study in Relapsing-Remitting Multiple Sclerosis (RRMS) (poster P04.219, Wednesday, April 14, 2010, 3:00 pm-7:30 pm EDT)

CLARITY study design

The CLARITY study was a two-year (96-week), randomized, double-blind, placebo-controlled, international trial. It randomized 1,326 patients with relapsing-remitting MS according to the revised McDonald criteria. Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of Cladribine Tablets or matching placebo tablets (1:1:1 ratio). Cladribine Tablets were given in two (3.5 mg/kg total dose) or four (5.25 mg/kg total dose) treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days (depending on patient weight), which means study patients took Cladribine Tablets for 8 to 20 days during the year. In the second year, two treatment courses were administered to all patient groups, meaning that patients took Cladribine Tablets for 8 to 10 days during the year.

The primary endpoint of the CLARITY study was the relapse rate over 96 weeks. Secondary endpoints included MRI endpoints, proportion of subjects relapse-free and disability progression at 96 weeks.

About Cladribine Tablets

EMD 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.

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 its two-year extension 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.

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 more than 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 EMD Serono, Inc.

EMD Serono, Inc., an affiliate of Merck KGaA, Darmstadt, Germany, is a leader in the US biopharmaceutical arena, integrating cutting-edge science with unparalleled patient support systems to improve people's lives. The company has strong market positions in neurodegenerative diseases, with Rebif® (interferon beta-1a), as well as in endocrinology, with Saizen® (somatropin (rDNA origin) for injection) and Serostim® (somatropin (rDNA origin) for injection). EMD Serono is a leader in reproductive health, with Gonal-f® (follitropin alfa for injection), Luveris® (lutropin alfa for injection) and Ovidrel® Prefilled Syringe (choriogonadotropin alfa injection). With a clear focus on the patient and a leadership presence in the biopharmaceutical industry, EMD Serono's US footprint continues to grow, with more than 1100 employees around the country and fully integrated commercial, clinical and research operations in the company's home state of Massachusetts.

For more information, please visit www.emdserono.com.

About Merck KGaA

Merck is a global pharmaceutical and chemical company with total revenues of ‚¬ 7.7 billion in 2009, a history that began in 1668, and a future shaped by approximately 33,000 employees in 61 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 www.merckserono.com or www.merck.de.

Contact: EMD Serono, Inc.
Heather Hatfield, 781-681-2124

 

Posted: April 2010

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