EU/3/12/1034: Orphan designation for the treatment of 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 haemoglobin and other 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.

At the time of designation, sickle-cell disease affected approximately 1.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 66,000 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 (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, the only medicine authorised in the EU to treat pain associated with sickle-cell disease was hydroxycarbamide. The main treatment for sickle-cell disease was blood transfusion and analgesics (medicines to relieve pain). This was usually combined with 'iron chelators' (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 it works in a different way to existing medicines, which may improve the blood flow to the organs. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains a monoclonal antibody (a type of protein), which has been designed to recognise and attach to a protein called 'P-selectin' that is present on the surface of the cells lining the blood vessels. P-selectin is thought to be involved in the attachment of sickle cells and inflammatory cells to the blood vessels, leading to the blockage of the blood flow and pain in patients with sickle-cell disease. By attaching to P-selectin, the medicine is expected to prevent the deposit of sickle and inflammatory cells in blood vessels, thereby allowing better blood flow and improving the symptoms of the disease.

The effects of humanised monoclonal antibody against P-selectin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for sickle-cell disease. Orphan designation of this medicine had been granted in the United States of America for the treatment of vaso-occlusive crisis in patients with sickle-cell disease.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 July 2012 recommending the granting of this designation.

• 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.