For doctors

What is it?

Fabrazyme is a solution for infusion (drip into a vein) containing the active substance agalsidase beta.

What is it used for?

Fabrazyme 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 (GL-3). If the enzyme is not present, GL-3 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.
Because the number of patients with Fabry disease is low, the disease is considered ‘rare’, and Fabrazyme 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 it used?

Only a doctor who has experience in treating patients with Fabry disease or other inherited metabolic diseases should give Fabrazyme. It is used as an intravenous infusion of 1 mg per kilogram body weight given once every two weeks. The starting infusion rate should be no more than 0.25 mg per minute (15 mg per hour) to reduce the risk of infusion-related side effects. The infusion rate may be increased gradually with further infusions. One study has looked at what happens to Fabrazyme when given to children and suggested that Fabrazyme could be used in children between eight and 16 years of age at the same dose. Patients who have severe kidney damage may have a weaker response to treatment. Fabrazyme is intended for long-term use.

How does it work?

Fabrazyme is an enzyme replacement therapy. Enzyme replacement therapies provide patients with the enzyme they are lacking. Fabrazyme is designed to replace the human enzyme alpha-galactosidase A, which people with Fabry disease are lacking. The active substance in Fabrazyme, agalsidase beta, 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 GL-3 and stops it building up (accumulating) in the patient’s cells.

How has it been studied?

Three clinical studies involving a total of 73 adult patients were presented. In the main study, Fabrazyme was compared with placebo (a dummy treatment) in 58 patients. The study looked at the effect of the medicines on clearing GL-3 from the kidney.
The effectiveness of Fabrazyme was also tested in 16 children aged between eight and 16 years who had Fabry disease.

What benefits has it shown during the studies?

In the main study, Fabrazyme produced a highly significant and almost complete clearance of GL-3 in the kidney cells after 20 weeks of treatment: 69% of the patients treated with Fabrazyme had the best score for clearance, compared with none of the patients in the placebo group. This might lead to the symptoms of the disease improving or the disease becoming stable.
Children treated with Fabrazyme also had decreases in levels of GL-3 in the blood, with all children having normal levels after 20 weeks of treatment. This was accompanied by improvements in the children’s symptoms and quality of life.

What is the risk associated?

The most common side effects with Fabrazyme (seen in more than 1 patient in 10) are caused by the infusion rather than the medicine. These reactions are mainly fever and chills. Other very common side effects include headache, paraesthesia (abnormal sensations like pins and needles), nausea (feeling sick), vomiting, flushing and feeling cold. Side effects reported in children are similar to those seen in adult patients. For the full list of all side effects reported with Fabrazyme, see the Package Leaflet.
Patients who receive Fabrazyme can develop antibodies (proteins that are produced in response to Fabrazyme and can affect treatment).
Fabrazyme should not be used in people who may be hypersensitive (allergic) to agalsidase beta or any of the other ingredients.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that, for patients with Fabry disease, treatment with Fabrazyme might provide long-term clinical benefits. The CHMP decided that Fabrazyme’s benefits are greater than its risks for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease. The Committee recommended that Fabrazyme be given marketing authorisation.
Fabrazyme 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 6 February 2008.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Fabrazyme to Genzyme Europe B.V. on 3 August 2001. The marketing authorisation was renewed on 3 August 2006.

The record of Fabrazyme’s designation as an orphan medicine is available here.

Name

Fabrazyme 35 mg, powder for concentrate for solution for
infusion

Composition

Each vial of Fabrazyme contains a nominal value of 35 mg of agalsidase beta. After reconstitution with 7.2 ml water for injections, each vial of Fabrazyme contains 5 mg/ml (35 mg/7 ml) of agalsidase beta. The reconstituted solution must be diluted further (see section 6.6).

Agalsidase beta is a recombinant form of human α-galactosidase A and is produced by recombinant DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid sequence of the recombinant form, as well as the nucleotide sequence which encoded it, are identical to the natural form of α-galactosidase.

Pharmaceutical Form

Powder for concentrate for solution for infusion
White to off-white lyophilized cake or powder