What is Replagal?
Replagal is a solution for infusion, which contains the active substance agalsidase alfa.
What is Replagal used for?
Replagal is used to treat patients with Fabry disease, a rare inherited condition.
Patients suffering from this disease present a deficiency of the enzyme alpha-galactosidase A. This enzyme normally breaks down the lipid globotriaosilceramide (Gb3). If this enzyme is missing, Gb3 cannot be broken down and accumulates in cells, for example in kidney cells.
Patients with Fabry disease may have extensive symptoms, including serious disorders such as kidney failure, heart problems and stroke.
As the number of patients with Fabry disease is low, this disease is considered "rare" and on 8 August 2000 Replagal was designated an "orphan medicine" (a medicine used to treat rare diseases).
The medicine can only be obtained with a prescription.
How is Replagal used?
Replagal should be administered under the supervision of a doctor who specializes in the treatment of Fabry disease or other hereditary metabolic disorders. It is given as an intravenous infusion of 0.2 mg / kg body weight for 40 minutes every 2 weeks. In some studies the effect of Replagal administered to children was examined and it was therefore suggested that Replagal can be used in children aged 7 to 18 at the same dose. Patients who have severe kidney problems have a minor response to treatment. Replagal is intended for long-term use.
How does Replagal work?
Replagal is an enzyme replacement therapy, which is a therapy that provides patients with the missing enzyme. Replagal is intended to replace the human enzyme alpha-galactosidase A, which people with Fabry disease are lacking. The active substance in Replagal, agalsidase alfa, is a copy of the human enzyme produced by a method called "recombinant DNA technology": the enzyme is produced by a cell in which a gene (DNA) has been introduced that the makes it capable of producing the enzyme. This replacement enzyme favors the breakdown of Gb3 by preventing its accumulation in the cells.
What studies have been performed on Replagal?
Replagal has been studied in two clinical studies, on a total of 40 male patients. Replagal was compared with a placebo (a dummy treatment); in one study its effect on pain was measured, while in another study its effect on the elimination of Gb3 from the left ventricle (myocardium) was examined. A study was also carried out on 15 female patients (carriers).
Replagal has also been studied in 24 children aged between six and a half and 18 years.
What benefit has Replagal shown during the studies?
After 6 months of therapy, Replagal significantly reduced pain in patients treated in comparison to those receiving placebo (a dummy treatment). Replagal produced an average reduction in left ventricular mass of 11.5 g, while placebo-treated patients experienced an increase of 21.8 g. These results indicate that the symptoms of the disease improve or that the disease remains stable. In women the effects were comparable to the results found in men. Children who received 6 months of treatment with Replagal did not show an increase in cardiac mass and Gb3 levels in the blood had decreased.
What is the risk associated with Replagal?
The most common side effects (seen in more than one patient in 10 during the studies) are caused by the infusion rather than by the medicine itself. These are mainly chills, headaches, nausea, pyrexia (fever), redness of the face and fatigue (tiredness), which are generally not serious. Other very common side effects include pain and discomfort. The side effects reported in children are similar to those seen in adults. For the full list of all side effects reported with Replagal, see the Package Leaflet.
Patients taking Replagal may develop antibodies (proteins produced as a reaction to Replagal, which may compromise treatment).
Replagal should not be used in people who may be hypersensitive (allergic) to agalsidase alfa or other ingredients in the medicine.
Why has Replagal been approved?
The Committee for Medicinal Products for Human Use (CHMP) has decided that for patients with Fabry disease, treatment with Replagal can produce long-term clinical benefits. The CHMP decided that Replagal's benefits are greater than its risks and recommended that it be given marketing authorization.
Replagal was authorized "in exceptional circumstances" because, as it is used to treat a rare disease, it was not possible to obtain more detailed information on the medicine. The European Medicines Agency (EMEA) reviews new information available every year and this summary will be updated as necessary.
What information is still awaited for Replagal?
The company that makes Replagal will carry out further studies on the medicine, especially to obtain the results of 5 years of therapy, other dosages, maintenance doses and studies on children.
More information on Replagal
On 3 August 2001, the European Commission granted a marketing authorization valid throughout the European Union for Replagal to TKT Europe AB. The marketing authorization was renewed on 3 August 2006. For registration of Replagal's status as an orphan medicinal product, click here.
For the full EPAR of Replagal, click here.
Last update of this summary: 02-2007
