Merck Serono Announces Outcome of Its Request for Reexamination of CHMP Opinion for Cladribine Tablets in MSBy Merck Serono S A, PRNE
Thursday, January 20, 2011
GENEVA, January 21, 2011 -
- CHMP Confirms its Initial Negative Opinion Regarding the Marketing Authorization Application for Cladribine Tablets - Merck Serono Remains Fully Committed to the Potential of Cladribine Tablets to Meet an Unmet Medical Need as an Oral, Short-Course, Disease-Modifying Drug for Multiple Sclerosis
Merck Serono, a division of Merck KGaA, Darmstadt, Germany,
announced today that following its request for reexamination, the Committee
for Medicinal Products for Human Use (CHMP) confirmed its previous position
and adopted a final negative opinion regarding the marketing authorization
application (MAA) for Cladribine Tablets as a treatment for
relapsing-remitting multiple sclerosis (MS).
The majority of CHMP members were of the opinion that the
benefits of Cladribine Tablets do not outweigh its risks based on data
submitted. However, some CHMP members did not share this opinion and voted in
favor of a conditional marketing authorization of Cladribine Tablets for the
indication discussed during the reexamination procedure.
"We are disappointed by the CHMP opinion however we continue
to believe that our data support Cladribine Tablets as a treatment option for
patients with relapsing forms of MS," said Dr. Bernhard Kirschbaum, Merck
Serono's Head of Research and Development. "We remain fully committed to the
potential of Cladribine Tablets to meet an unmet medical need as an oral,
short-course, disease-modifying drug for multiple sclerosis and will evaluate
our options for bringing this therapeutic option to patients who could
benefit from it also in Europe."
Merck Serono remains committed to completing the ongoing
clinical trials with Cladribine Tablets. The Data Safety Monitoring Board
that independently oversees the conduct of these trials recently concluded
that they should continue. These trials, which are fully enrolled, will
provide additional information on the efficacy and safety of Cladribine
Tablets in MS. Top-line results from the CLARITY(1) EXTENSION and ORACLE
MS(2) studies are expected by the end of 2011. Top-line results from the
ONWARD(3) study are expected in the first half of 2012.
Cladribine Tablets are approved and available under the trade
name Movectro(R) in Australia and Russia as a treatment of
relapsing-remitting MS and are under regulatory review in other countries,
including the United States where the application has been granted Priority
Review by the Food and Drug Administration (FDA). Cladribine Tablets
registration applications are supported by the results from the CLARITY
study, involving over 1,300 patients with relapsing-remitting multiple
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
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
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 efficacy 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 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. - 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, 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 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 Merck Serono
Merck Serono is the biopharmaceutical division of Merck KGaA,
Darmstadt, Germany, a global pharmaceutical and chemical company.
Headquartered in Geneva, Switzerland, Merck Serono discovers, develops,
manufactures and markets prescription medicines of both chemical and
biological origin in specialist indications. In the United States and Canada,
EMD Serono operates as a separately incorporated affiliate of Merck 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 alfa), endocrine and metabolic disorders
(Saizen(R) and Serostim(R), somatropin), (Kuvan(R), sapropterin
dihydrochloride) as well as cardiometabolic diseases (Glucophage(R),
metformin), (Concor(R), bisoprolol), (Euthyrox(R), levothyroxine). Not all
products are available in all markets.
With an annual R&D expenditure of over EUR 1bn, Merck Serono
is committed to growing its business in specialist-focused therapeutic areas
including neurodegenerative diseases, oncology, fertility and endocrinology,
as well as new areas potentially arising out of research and development in
Merck is a global pharmaceutical and chemical company with
total revenues of EUR 7.7 billion in 2009, a history that began in 1668, and
a future shaped by approximately 40,000 employees in 64 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
Merck Serono S.A. - Geneva, 9 Chemin des Mines, 1202 Genève, Suisse, Media relations, Tel: +41-22-414-36-00
Tags: Geneva, January 21, Merck Serono S A, Switzerland