EU/3/02/092: Orphan designation for the treatment of chronic iron overload requiring chelation therapy

Chronic iron overload is a condition due to man's inability to actively eliminate iron from the body. Chronic iron accumulation is mainly consecutive to either excess intestinal absorption (hemochromatosis) or excess administration through repetitive transfusions (iron contained in red blood cells). Repeated transfusions can be necessary in patients presenting chronic anaemias (e.g. thalassemia, sickle cell anaemia).

Chronic iron overload is a serious condition. Complications are related to iron deposits in tissues which can induce organ failure. This condition is life-threatening when the heart or the liver is affected.

At the time of designation, chronic iron overload requiring chelation therapy affected approximately 2.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 103,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union. At the time of designation, this represented a population of 380,600,000 (Eurostat 2002).

Phlebotomy (blood removal by venipuncture) is the first-choice therapy for haemochromatosis, except when blood removal is impossible. For such patients, or for patients with transfusion-dependent anaemias, iron overload can be treated by administration of iron chelators.Two medicinal products which chelate iron had been authorised in the Community at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that deferasirox might be of potential significant benefit for the treatment of chronic iron overload, particularly in terms of its pharmacological properties.

Deferasirox is an iron chelator. Iron chelators are molecules binding to iron in the body, allowing it to then be eliminated through urinary or intestinal routes at a higher rate than the natural very low iron elimination rate (through shedding of skin and mucosal cells, menstruation or other blood loss).

At the time of submission of the application for orphan designation, clinical trials were ongoing in patients presenting iron overload after repeated transfusions for chronic anaemias.

Deferasirox had not been marketed anywhere worldwide or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 January 2002 recommending the granting of this designation.

Update: 4-(3,5-Bis(hdroxy-phenyl)-1,2,4) triazol-1-yl) benzoic acid (Exjade) has been authorised in the EU since 28 August 2006 for treatment of chronic iron overload due to frequent blood transfusions ( >/= 7 ml/kg/month of packed red blood cells) in patients with beta thalassaemia major aged 6 years and older.

Treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups:

• in patients with other anaemias,
• in patients aged 2 to 5 years,
• in patients with beta thalassaemia major with iron overload due to infrequent blood transfusions (7ml/kg/month of packed red blood cells).

More information on Exjade can be found in the European public assessment report (EPAR) on the Agency's website.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.