On 12 March 2013, orphan designation (EU/3/13/1112) was granted by the European Commission to Theradex (Europe) Ltd, United Kingdom, for poloxamer 188 for the treatment of sickle-cell disease.
- What is sickle-cell disease?
Sickle-cell disease is a genetic disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped (like a sickle). The change in shape is caused by the presence of an abnormal form of haemoglobin, the protein in red blood cells that carries oxygen around the body. In patients with sickle-cell disease, the abnormal red blood cells attach to the walls of blood vessels and block them, restricting the flow of oxygen-rich blood to the internal organs such as the heart, lungs and spleen. The abnormal red blood cells have also a shorter life span and release toxic molecules into the blood circulation. As a result, patients with the disease have severe pain and damage to multiple organs as well as repeated infections and anaemia (low red-blood-cell counts).
Sickle-cell disease is a severe disease that is long-lasting and may be life-threatening because of damage to the heart and the lungs, anaemia and infections.
- What is the estimated number of patients affected by the condition?
At the time of designation, sickle-cell disease affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 people*, which was considered to be 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 (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).
- What treatments are available?
At the time of designation, Siklos (hydroxycarbamide) was authorised in the EU to prevent recurrent, painful vaso-occlusive crises (that happen when blood vessels become blocked) in patients with sickle-cell disease. The main treatment for sickle-cell disease was blood transfusion and analgesics (medicines to relieve pain). This was usually combined with ‘iron-chelator’ medicines used to reduce the high iron levels in the body caused by repeated blood transfusions, which are necessary in patients with long-term anaemias such as sickle-cell disease. In some cases, haematopoietic (blood) stem-cell transplantation was used (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow) to allow the patient to produce red blood cells containing normal haemoglobin.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with sickle-cell disease because early studies suggest it may be used in addition to other treatments to control sudden episodes of blood-vessel blockage and reduce their duration. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
- How is this medicine expected to work?
Poloxamer 188 is a molecule thought to have the ability to attach to and seal the damaged surface of cells. In sickle-cell disease, the medicine is thought to attach to sickle cells, reducing their rigidity and their tendency to stick to the walls of blood vessels. This is expected to prevent the blockage of blood vessels by sickle cells, thereby allowing better blood flow and improving the symptoms of the disease.
- What is the stage of development of this medicine?
At the time of submission of the application for orphan designation, the evaluation of the effects of poloxamer 188 in experimental models was ongoing.
At the time of submission, clinical trials with poloxamer 188 in patients with sickle-cell disease were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for sickle cell disease. Orphan designation of poloxamer 188 has been granted in the United States for treatment of sickle-cell disease (this includes the treatment and prevention of complications of sickle-cell disease).
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 2013 recommending the granting of this designation.
- Opinions on orphan medicinal product designations are based on the following three criteria:
- 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.
|Name||Language||First published||Last updated|
|EU/3/13/1112: Public summary of opinion on orphan designation: Poloxamer 188 for the treatment of sickle-cell disease||(English only)||05/04/2013|
|Active substance||Poloxamer 188|
|Disease/condition||Treatment of sickle-cell disease|
|Date of decision||12/03/2013|
|Orphan decision number||EU/3/13/1112|
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
Sponsor's contact details
Theradex (Europe) Ltd
7 Pelham Court
Tel. +44 (0)129 3510 319
Fax +44 (0)129 3510 322
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
- Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
- European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.