EMA/81812/2013 EMEA/H/C/000670

EPAR summary for the public

Exjade
deferasirox

This is a summary of the European public assessment report (EPAR) for Exjade. 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 Exjade.

What is Exjade?
Exjade is a medicine that contains the active substance deferasirox. It is available as dispersible tablets that are mixed with a liquid to make up a suspension that the patient can drink. Each tablet contains 125 mg, 250 mg or 500 mg of deferasirox.

What is Exjade used for?

Exjade is used to treat chronic iron overload (an excess of iron in the body) in the following groups of patients: patients from six years of age who have beta thalassaemia major (an inherited blood disorder in which patients do not have enough haemoglobin in the blood) and who receive frequent blood transfusions; children with beta thalassaemia major aged from two to five years who receive frequent blood transfusions, when deferoxamine (another medicine used to treat iron overload) cannot be used or is inadequate; patients from two years of age with beta thalassaemia major who receive infrequent blood transfusions, when deferoxamine cannot be used or is inadequate; patients from two years of age who suffer from different types of anaemia (low levels of haemoglobin in the blood) who receive blood transfusions, when deferoxamine cannot be used or is inadequate;

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European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged.

patients from 10 years of age with non-transfusion-dependent thalassaemia syndromes, when deferoxamine cannot be used or is inadequate. Non-transfusion-dependent thalassaemia syndromes are blood disorders similar to beta thalassaemia major but which do not require blood transfusions. In these patients iron overload is caused by excess absorption of iron from the gut.

Because the number of patients with chronic iron overload is low, the disease is considered rare, and Exjade was designated an orphan medicine (a medicine used in rare diseases) on 13 March 2002. The medicine can only be obtained with a prescription.

How is Exjade used?

Treatment with Exjade should be started and supervised by a doctor who is experienced in the treatment of chronic iron overload. For chronic iron overload due to blood transfusions, the treatment starts once the patient has received about 100 ml of packed red blood cells per kilogram body weight, or once there are signs of iron overload (when the levels in the blood of ferritin, the protein in the body that stores iron, are over 1 mg per litre). The treatment usually starts using a dose of 20 mg per kilogram body weight (mg/kg). Starting doses of 10 or 30 mg/kg can also be used, depending on the frequency of the patients transfusions. These doses are then adjusted as needed, every three to six months, according to the response. In patients with non-transfusion-dependent thalassaemia syndromes, treatment is started when there is evidence of iron overload, and the recommended starting dose is 10 mg/kg. The dose is then adjusted as needed, every three to six months, according to the response. Treatment should be stopped once satisfactory iron levels are achieved. Exjade is taken every day, preferably at the same time each day, on an empty stomach (at least 30 minutes before food). The number of tablets of each strength that make up a dose is calculated based on the patients weight. The tablets are dispersed by stirring them in a glass of water or fruit juice to make a suspension for the patient to drink.

How does Exjade work?

The active substance in Exjade, deferasirox, is an iron chelator. It attaches to excess iron in the body to form a compound called a chelate that can be excreted by the body, mainly in the stools. This helps to correct the iron overload and prevent damage to organs such as the heart or liver due to excess iron.

How has Exjade been studied?

In chronic iron overload due to blood transfusions, Exjade was investigated in one main study comparing Exjade with deferoxamine in 591 patients with beta thalassaemia major. About half of the patients were under the age of 16, and 56 were less than six years old. The doctor and patients knew which medicine they were using because Exjade is given by mouth but deferoxamine is given by subcutaneous infusion (very slow injection under the skin) overnight. The effectiveness was measured by looking at the level of iron contained in the liver before and after one year of treatment with the medicines. An additional study looked at the effectiveness of Exjade in 184 patients who could not be treated with deferoxamine, including patients with beta thalassaemia major and with other types of anaemia.

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Exjade was also investigated in one main study involving 166 patients (including 21 patients aged from 10 to 18 years) from 10 years of age with non-transfusion-dependent thalassaemia syndromes and iron overload. In this study, Exjade was compared with placebo (a dummy treatment) and the main measure of effectiveness was the change in iron levels in the liver after 12 months of treatment.

What benefit has Exjade shown during the studies?

At the end of the main study in chronic iron overload due to blood transfusions, 53% of the patients receiving Exjade had shown a sufficient response to treatment, compared with 66% of the patients receiving deferoxamine. This indicates that Exjade may not have been as effective as the comparator medicine. However, when looking at the 381 patients who had particularly high levels of iron in their liver at the beginning of the study and who received comparable amounts of Exjade or deferoxamine, the two medicines were as effective as each other. There were too few patients in this study aged below six years to demonstrate the safety and effectiveness of Exjade in this age group. In the additional study, more than half of the patients who could not be treated with deferoxamine had responded to treatment with Exjade after a year, including patients aged between two and five years. In the study in patients with non-transfusion-dependent thalassaemia syndromes, Exjade was shown to be more effective than placebo at reducing iron levels in the liver: in patients treated with Exjade (at a starting dose of 10 mg/kg/day) liver iron levels decreased on average by 3.8 mg per gram of liver compared with an average increase of 0.4 mg per gram of liver in patients treated with placebo.

What is the risk associated with Exjade?

The most common side effect with Exjade (seen in more than 1 patient in 10) is increased blood creatinine (a marker of kidney problems). For the full list of all side effects reported with Exjade, see the package leaflet. Exjade must not be used in people who are hypersensitive (allergic) to deferasirox or any of the other ingredients, or in people whose creatinine clearance (a measure of the ability of the kidney to remove creatinine from the blood) is below 60 ml per minute. It must not be used in combination with other iron chelators. It is very important that the patients kidneys and liver are checked with blood tests before treatment with Exjade is started, and regularly during treatment. The dose should be reduced or treatment interrupted if a patient develops kidney or liver problems. Exjade is not recommended for patients with severe liver problems as it has not been tested in these patients.

Why has Exjade been approved?

The CHMP decided that Exjades benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe use of Exjade?
The company that makes Exjade must prepare an education pack for doctors, which is distributed whenever the medicine is launched. This pack will ensure that doctors know about the need to monitor the patients health, especially kidney function, when they prescribe the medicine. The company will also prepare a similar pack for patients. The company will also provide information to doctors who use the medicine to treat patients with nontransfusion-dependent thalassaemia syndromes, to ensure that they know about the risks and treatment recommendations for this group of patients.
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The company will perform a study in children aged 10 years and above with non-transfusiondependent thalassaemia to obtain more information on the long-term effects of treatment in these patients.

Other information about Exjade

The European Commission granted a marketing authorisation valid throughout the European Union for Exjade on 28 August 2006. The summary of opinion of the Committee for Orphan Medicinal Products for Exjade can be found on the Agencys website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations. The full EPAR for Exjade can be found on the Agencys website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Exjade, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. This summary was last updated in 01-2013.

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