Download Replagal, INN-agalsidase alfa

European Medicines Agency
EMEA/H/C/369
EUROPEAN PUBLIC ASSESSMENT REPORT (EPAR)
REPLAGAL
EPAR summary for the public
This document is a summary of the European Public Assessment Report (EPAR). It explains how the
Committee for Medicinal products for Human Use (CHMP) assessed the studies performed, to reach
their recommendations on how to use the medicine.
If you need more information about your medical condition or your treatment, read the Package
Leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information
on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).
What is Replagal?
Replagal is a solution for infusion into the body containing the active substance agalsidase alfa.
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, alpha-galactosidase A. This enzyme normally breaks down
a fatty substance called globotriaosylceramide (Gb3). If the enzyme is not present, Gb3 cannot be
broken down and it builds up in the 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.
Because the number of patients with Fabry disease is low, the disease is considered ‘rare’, and
Replagal was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 8 August 2000.
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. It is used as an intravenous infusion of 0.2 mg/kg body weight over 40
minutes given once every 2 weeks. Some studies have looked at what happens to Replagal when given
to children, and they suggested that Replagal could be used in children between 7 and 18 years of age
at the same dose. Patients who have severe kidney damage may have a weaker response to treatment.
Replagal is intended for long-term use.
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 people with Fabry disease are lacking. 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 a cell that has received a gene (DNA), which makes it able to produce the enzyme. The
replacement enzyme helps to break down the Gb3 and stops it building up (accumulating) in the cells.
7 Westferry Circus, Canary Wharf, London E14 4HB, UK
Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 68
E-mail: [email protected] http://www.emea.europa.eu
©EMEA 2007 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged
How has Replagal been studied?
Replagal has been examined in two clinical studies, involving a total of 40 male patients. Replagal
was compared with a placebo (a dummy treatment) and its effect on pain was measured in one study
and its effect on clearing Gb3 from the left ventricle (heart muscle) was studied in the other. A further
study was also carried out in 15 female (carrier) patients. Replagal has also been studied in 24 children
aged between 6 and a half and 18 years of age.
What benefit has Replagal shown during the studies?
After 6 months of therapy Replagal significantly reduced pain in patients when compared to placebo
(dummy) treated patients. 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. These results suggest the
symptoms of the disease improving or the disease becoming stable. The effects in female patients
were shown to be comparable to the results seen in male patients. Children who received 6-month
treatment with Replagal had no increase in heart, and the levels of Gb3 in their blood was reduced.
What is the risk associated with Replagal?
During the studies the most common side effects (seen in more than 1 patient in 10) are caused by the
infusion rather than the medicine. These reactions are mainly chills, headache, nausea, pyrexia (fever),
flushing and fatigue (tiredness), and are rarely severe. Other very common side effects were pain and
discomfort. Side effects reported in children are similar to those seen in adult patients. For the full list
of all side effects reported with Replagal, see the Package Leaflet.
Patients who receive Replagal can develop antibodies (proteins that are produced in response to
Replagal and can affect treatment).
Replagal should not be used in people who may be hypersensitive (allergic) to agalsidase alfa or any
of the other ingredients.
Why has Replagal been approved?
The Committee for Medicinal products for Human Use (CHMP) decided that for patients with Fabry
disease, treatment with Replagal might provide long-term clinical benefits. The CHMP decided that
Replagal’s benefits are greater than its risks and recommended that Replagal be given marketing
authorisation.
Replagal has been authorised under "Exceptional Circumstances", because, as the disease is rare, it has
not been possible to obtain complete information on the medicine. Every year, the European
Medicines Agency (EMEA) reviews any new information that may have become available and this
summary will be updated as necessary.
What information is still awaited for Replagal?
The company that makes Replagal will carry further studies with the medicine, looking in particular at
the results of 5-year treatment, other dosages, maintenance dosages, and studies in children.
Other information about Replagal:
The European Commission granted a marketing authorisation valid throughout the European Union
for Replagal to TKT Europe AB on 3 August 2001. The marketing authorisation was renewed on
3 August 2006.
The record of Replagal’s designation as an Orphan medicine is available here.
The full EPAR for Replagal is available here.
This summary was last updated in 02-2007.
©EMEA 2007
2/2