Merck Serono: REFLEX Study Results Show Treatment With Rebif(R) Delays Conversion to MS in Patients With First Clinical Signs of the Disease

By Merck Serono, PRNE
Sunday, October 24, 2010

Study Met its Primary Endpoint

GENEVA, October 25, 2010 - Merck Serono, a division of Merck KGaA, Darmstadt, Germany,
announced today that the two-year Phase III REFLEX 1 study met its primary
endpoint by demonstrating that Rebif(R) (interferon beta-1a) significantly
delayed conversion to multiple sclerosis (MS) diagnosed according to the
McDonald criteria 2 in patients with a first clinical event suggestive of the

The international REFLEX study with 517 patients was conducted
with the serum-free formulation of Rebif(R) 3, which was first introduced in
2007 and 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 serum-free formulation of Rebif(R) is
currently not available in the United States.

The risk of conversion to MS (McDonald criteria) over two
years was reduced by 51% (p<0.00001) in patients who received Rebif(R) 44 mcg
three times a week compared to placebo. A risk reduction of 31% (p=0.008)
compared to placebo was observed in patients who received once-weekly
administration of Rebif(R) 44 mcg. The probability of conversion to MS
(McDonald criteria) over two years was 86% in the placebo group, 62% in
patients who received Rebif(R) 44 mcg three times a week and 76% in patients
who received once-weekly administration of Rebif(R) 44 mcg.

"We are committed to provide treatments that meet the
individual needs of people living with multiple sclerosis at the various
stages of the disease," said Dr. Roberto Gradnik, Executive Vice President
for Neurodegenerative Diseases at Merck Serono. "Over the years we have
continuously worked on enhancing the product profile of Rebif(R) with new
formulations, new injection devices and new clinical data. We are very
pleased with these new clinical data as they show that patients in the study
with the first clinical signs of multiple sclerosis benefited from treatment
with Rebif(R)."

The safety profile of Rebif(R) observed in the REFLEX study was similar
to that seen in other recent studies with the serum-free formulation of
Rebif(R). No unexpected adverse reactions were identified. The majority of
adverse events were mild or moderate. The most frequent undesirable effect
was flu-like symptoms, which is typical of interferon therapy; most were mild
in severity. Flu-like symptoms are transient and can be managed with
prophylactic treatment.

Full results of the REFLEX study will be submitted for presentation at
upcoming scientific meetings.

A three-year double blind extension of the REFLEX study, called REFLEXION
4, is currently ongoing in order to provide long-term follow-up data (up to
five years).

1 REFLEX: REbif FLEXible dosing in early multiple sclerosis

2 The primary endpoint of the REFLEX study was time to
conversion to MS according to the revised McDonald criteria (2005). The
McDonald criteria are the current reference criteria for the diagnosis of MS.
According to the McDonald criteria, 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 In previous communications, the serum-free formulation of
Rebif(R) was referred to as the "new 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 experience 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 conversation to Mc Donald MS".
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

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

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 division for innovative prescription
pharmaceuticals of Merck KGaA, Darmstadt, Germany, a global pharmaceutical
and chemical company. Headquartered in Geneva, Switzerland, Merck Serono
discovers, develops, manufactures and markets innovative small molecules and
biopharmaceuticals to help patients with unmet medical needs. In the United
and Canada, EMD Serono operates through separately incorporated

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 more than EUR 1 billion,
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 autoimmune and inflammatory diseases.

About Merck

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 (including Merck Millipore) 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 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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