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

GENEVA, June 29, 2011 /PRNewswire/ --

• 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 Kirschbaum, 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 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), (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 http://www.merckserono.com or http://www.merck.de