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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/145978/2016

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 film-coated

tablets (90, 180 and 360 mg) and as dispersible tablets (125, 250 and 500 mg). The dispersible

tablets are to be mixed with a liquid to make up a suspension that the patient can drink.

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 6 years of age who have beta thalassaemia major (an inherited blood disorder in which patients do not have enough normal haemoglobin in the blood) and who receive frequent blood transfusions;

•    children aged 2 to 5 years with beta thalassaemia major who receive frequent blood transfusions, when deferoxamine (another medicine used to treat iron overload) cannot be used or is inadequate;

•    patients from 2 years of age with beta thalassaemia major who receive infrequent blood transfusions, when deferoxamine cannot be used or is inadequate;

•    patients from 2 years of age who suffer from other 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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• 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, treatment with Exjade starts after the patient has received about 100 ml of packed red blood cells per kilogram body weight or when there are signs of iron overload (such as the levels in the blood of ferritin, the protein in the body that stores iron, rising over 1 mg per litre). In patients with non-transfusion-dependent thalassaemia syndromes, treatment is started when there is evidence of iron overload. The starting dose depends on the patient's body weight, on whether the patient is taking the film-coated tablet or the dispersible tablet and on the total amount of transfusion the patient has received. The dose is then adjusted as needed, every 3 to 6 months, according to the response.

Exjade is taken once a day. The dispersible tablets should be taken on an empty stomach (at least 30 minutes before food) whereas the film-coated tablets can be taken with a light meal. For further information, see the package leaflet.

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 'chelate' that can be excreted by the body, mainly in the stool. 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 6 years old. The effectiveness was determined by the level of iron 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.

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 and deferoxamine, the two medicines were as effective as each other. There were too few patients in this study aged below 6 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 2 and 5 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).

Exjade must not be used 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 patient's 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.

For the full list of all side effects and restrictions with Exjade, see the package leaflet.

Why has Exjade been approved?

The CHMP decided that Exjade's 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?

A risk management plan has been developed to ensure that Exjade is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Exjade, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that makes Exjade must prepare an education pack for healthcare professionals. This pack aims to inform them about the risks and treatment recommendations with Exjade, including choosing the right dose, that the doses are different for the film-coated tablets and dispersible tablets, and the need to monitor the patient's health, especially kidney function. The company will also prepare a similar pack for patients.

Finally, the company will perform the following studies: a study comparing the benefits of the film-coated tablets with the dispersible tablets; a study in children aged 10 years and above with nontransfusion-dependent thalassaemia to obtain more information on the long-term effects of treatment in these patients; and a study to assess the safety of the film-coated tablets (particularly when they are crushed) in children.

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 Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations.

The full EPAR for Exjade can be found on the Agency's 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 03-2016.

Exjade

EMA/145978/2016

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