The European Commission (EC) has approved extension of the indication of Rebif (interferon beta-1a), Merck Serono’s, leading treatment for relapsing forms of multiple sclerosis (MS). This EC approval is for the use of Rebif 44 micrograms three times weekly 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. This approval was based on the results of the REFLEX study, which showed the safety and efficacy of Rebif in this patient population.

Rebif (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 in chronic progressive MS has not been established. Interferons are thought to help reduce inflammation. The exact mechanism is unknown.

“We are delighted by the European Commission decision,” said Dr Annalisa Jenkins, Head of Global Drug Development and Medical at Merck Serono. “Multiple sclerosis has an initial stage when clinical manifestations are not pronounced but irreversible neurological damage is taking place. Throughout the European Union, neurologists will now be able to prescribe Rebif for patients with early signs of this devastating disease.”

The new labelling for Rebif is valid immediately in all 27 member states of the European Union.

Merck Serono has a long-standing commitment to the therapeutic area of MS. The company continues to invest in discovering and developing treatment options in this area, including active life-cycle management initiatives for Merck Serono’s foundation therapy, Rebif. In addition, the company continues to strengthen existing, and establish new collaborations to advance research and bring innovative solutions to patients living with MS.

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 44 micrograms three times weekly, Rebif 44 micrograms once weekly, 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 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 MRI brain scans and clinical relapses. The REFLEX study was conducted with the human serum albumin (HSA)-free formulation of Rebif, which is not available in the United States.

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


Rebif, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 90 countries worldwide. Rebif has been proven to delay the progression of disability, reduce the frequency of relapses and reduce MRI lesion activity and area. Rebif is available in a 22 micrograms and 44 micrograms ready-to-use pre-filled syringe and a titration pack (8.8 micrograms). Rebif 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 electronic auto-injection device, in several EU member countries, Switzerland and Canada, as well as in Australia. RebiDose™, a single-use disposable pen, which is pre-filled with Rebif, is approved in the European Union, Australia and Canada, and was launched in several EU member countries in 2011. RebiSmart and RebiDose are not available in the United States.

Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company.