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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/458725/2015

EMEA/H/C/000369

EPAR summary for the public

Replagal

agalsidase alfa

This is a summary of the European public assessment report (EPAR) for Replagal. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Replagal.

What is Replagal?

Replagal is medicine that contains the active substance agalsidase alfa. It is available as a concentrate to be made into solution for infusion (drip) into a vein.

What is Replagal used for?

Replagal is used to treat patients who have Fabry disease, a rare inherited disorder. Patients with Fabry disease do not have enough of an enzyme called alpha-galactosidase A. This enzyme normally breaks down a fatty substance called globotriaosylceramide (Gb3 or GL-3). If the enzyme is not present, Gb3 cannot be broken down and it builds up in the body's cells, such as kidney cells.

People with Fabry disease may have a wide range of signs and symptoms, including severe conditions such as kidney failure, heart problems, and stroke.

The medicine can only be obtained with a prescription.

How is Replagal used?

Only a doctor who has experience in treating patients with Fabry disease or other inherited metabolic diseases should give Replagal.

Replagal is given once every 2 weeks as an infusion of 0.2 mg per kilogram body weight over 40 minutes. It is intended for long-term use.

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How does Replagal work?

Replagal is an enzyme replacement therapy. Enzyme replacement therapy provides patients with the enzyme they are lacking. Replagal is designed to replace the human enzyme alpha-galactosidase A, which is lacking in people with Fabry disease. The active substance in Replagal, agalsidase alfa, is a copy of the human enzyme, produced by a method known as 'recombinant DNA technology': it is made by cells that have received a gene (DNA), which makes them able to produce the enzyme. The replacement enzyme helps to break down the Gb3 and stops it building up in the cells.

How has Replagal been studied?

Replagal has been compared with placebo (a dummy treatment) in two main studies involving a total of 40 male patients. The first study measured the effects of Replagal on pain while the second study measured its effect on the mass of the left ventricle (heart muscle), a measure of the amount of Gb3 in the heart cells. The effect of giving doses weekly rather than every two weeks was also investigated. A further study was carried out in 15 female patients. Replagal has also been evaluated in additional studies involving 38 children aged 7 years or above.

What benefit has Replagal shown during the studies?

After 6 months of treatment, Replagal significantly reduced pain in patients compared with placebo. Replagal reduced left ventricle mass by an average of 11.5 g while patients receiving placebo had an increase in left ventricular mass of 21.8 g. The effects in female patients were comparable to those in male patients and weekly dosing had no advantage over standard doses. Children who received Replagal had no unexpected increase in heart mass, and the levels of Gb3 in their blood were reduced.

What is the risk associated with Replagal?

The most common side effects with Replagal (seen in more than 1 patient in 10) are infusion-associated reactions. These include chills, headache, nausea, pyrexia (fever), pain and discomfort, flushing and fatigue (tiredness), and are rarely severe. For the full list of all side effects and restrictions with Replagal, see the package leaflet.

Why has Replagal been approved?

The CHMP decided that for patients with Fabry disease treatment with Replagal might provide longterm clinical benefits. The CHMP decided that Replagal's benefits are greater than its risks and recommended that it be given marketing authorisation.

Replagal was originally authorised under 'exceptional circumstances', because as the disease is rare, limited information was available at the time of approval. As the company had supplied the additional information requested, the 'exceptional circumstances' ended on 20 July 2015.

Other information about Replagal

The European Commission granted a marketing authorisation valid throughout the European Union for Replagal on 3 August 2001.

The full EPAR for Replagal can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about

Replagal

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treatment with Replagal, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2015.

Replagal

EMA/458725/2015