Merck Serono Submits Application for Extension of Indication for Rebif(R) in Europe

By Merck Serono S A, PRNE
Tuesday, June 28, 2011

GENEVA, June 29, 2011 -

  • Extended Indication would Include Patients with Early Signs
    of Multiple Sclerosis

Merck Serono, a division of Merck KGaA, Darmstadt, Germany,
announced today that it has submitted an application to the
European Medicines Agency (EMA) to extend the indication of
Rebif[R], its leading treatment for multiple sclerosis
(MS). The requested label extension is for the use of
Rebif[R] in patients who have experienced a single
demyelinating event, an early sign of the disease, and who are at
high risk of converting to MS.

“Our application to extend the indication of Rebif[R]
is based on the REFLEX[1] study, which focused on
patients with early signs of multiple sclerosis,” said Dr. Bernhard
, Executive Vice President for Global Research and
Development at Merck Serono. “We remain strongly committed to
addressing the medical needs of patients with multiple sclerosis at
the various stages of this devastating disease.”

Merck Serono’s submission of a type II variation to extend the
indication of Rebif[R] is supported by results of the
REFLEX study, which were presented at the American Academy of
Neurology (AAN) in April 2011. The REFLEX study was designed to
evaluate the effect of two different doses of Rebif - the currently
approved 44mcg three times a week and 44mcg once a week - versus
placebo, on the “Time to conversion to McDonald MS
(2005)[2]” in patients with a first clinical
demyelinating event and having magnetic resonance imaging (MRI)
brain scans consistent with early signs of MS. The study met its
primary endpoint for both doses by demonstrating that
Rebif[R] significantly delayed conversion to McDonald MS
(2005) in those patients.

The REFLEX study was conducted with the
HSA-free[3] formulation of
Rebif[R], which is now available in all European Union
countries, Australia, Canada and Switzerland, as well as a number
of countries in Asia, Latin America, Africa and the Middle East.
The HSA-free formulation of Rebif[R] is
currently not available in the United States.

[1 ]REFLEX: REbif FLEXible dosing
in early multiple sclerosis

[2 ] The McDonald criteria are criteria for the
diagnosis of MS. According to the McDonald criteria (2005), the
diagnosis of MS is based on one attack and subsequent dissemination
of lesions evidenced by either a positive magnetic resonance
imaging (MRI) scan or a new clinical relapse.

[3 ]HSA-free formulation of
Rebif[R] = human serum albumin-free
formulation of Rebif[R]

About the REFLEX study design

The REFLEX study was a two-year (24-month), randomized,
double-blind, placebo-controlled, international Phase III trial. It
randomized 517 patients considered at risk of developing MS due to
a recently experienced isolated demyelinating event (e.g. optic
neuritis, myelopathy or brainstem syndrome) and having magnetic
resonance imaging (MRI) brain scans consistent with early signs of
MS. Study participants were randomized in a 1:1:1 ratio to receive
either Rebif[R] 44 mcg three times a week,
Rebif[R] 44 mcg once a week, or placebo as a
subcutaneous injection. Patients were treated for a period of two
years, or up to the time when they experienced a second attack
leading to a diagnosis of clinically definite MS. At this point,
patients were offered open-label treatment with Rebif[R]
44 micrograms three times a week. The primary endpoint of the study
was “time to conversion to McDonald MS (2005)”. Further endpoints
include “time to conversion to clinically definite MS” (the main
secondary endpoint), assessments of magnetic resonance imaging
(MRI) brain scans and clinical relapses.

About Rebif [R]

Rebif[R] (interferon beta-1a) is a
disease-modifying drug used to treat relapsing forms of multiple
sclerosis (MS) and is similar to the interferon beta protein
produced by the human body. The efficacy of
Rebif[R] in chronic progressive MS has not
been established. Interferons are thought to help reduce
inflammation. The exact mechanism is unknown.

Rebif[R], which was approved in Europe in
1998 and in the US in 2002, is registered in more than 90 countries
worldwide. Rebif[R] has been proven to delay
the progression of disability, reduce the frequency of relapses and
reduce MRI lesion activity and area*.
Rebif[R] is available in a 22 micrograms and
44 micrograms ready-to-use pre-filled syringe and a titration pack
(8.8 micrograms). Rebif[R] is also now
available in two multidose cartridges [132 micrograms (three doses
of 44 micrograms) and 66 micrograms (three doses of 22 micrograms)]
for the use with the RebiSmart[TM] device, in several EU member
countries, Switzerland and Canada, as well as in Australia.

Rebif[R] should be used with caution in
patients with a history of depression, liver disease and seizures.
Most commonly reported side effects are flu-like symptoms,
injection site disorders, elevation of liver enzymes and blood cell
abnormalities. Patients, especially those with depression, seizure
disorders, or liver problems, should discuss treatment with
Rebif[R] with their doctors.

* The exact correlation between MRI findings and the current or
future clinical status of patients, including disability
progression, is unknown.

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

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), (Egrifta[TM],
tesamorelin), 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 € 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 rheumatology.

About Merck

Merck is a global pharmaceutical and chemical company with total
revenues of € 9.3 billion in 2010, a history that began in 1668,
and a future shaped by more than 40,000 employees in 67 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 or

Merck Serono S.A. – Geneva, 9 Chemin des Mines, 1202 Genève, Suisse, Media relations, Tel: +41-22-414-36-00

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