EU/3/18/1991: 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 other blood cells and 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. Because the abnormal red blood cells have a shorter life span, they release haemoglobin into the blood circulation rather than carrying it to the internal organs where it is needed. As a result, patients experience severe pain as well as repeated infections and anaemia (low red blood cell counts).

Sickle cell disease is a life-long disease 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 2 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 (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide (hydroxyurea). The main treatment for sickle cell disease was blood transfusion. This was usually combined with 'iron chelators' (medicines used to reduce high iron levels in the body resulting from repeated blood transfusions). In some cases, haematopoietic (blood) stem cell transplantation was used. This is a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor to form new bone marrow that produces healthy 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 show that adding this medicine to treatment with hydroxycarbamide can further reduce the occurrence of vaso-occlusive crises (when blood vessels become blocked by the abnormal red blood cells, restricting the flow of blood to an organ). This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of docosahexaenoic acid (DHA), an omega-3 fatty acid, which is an important component of the membrane of many cells, including red blood cells.

It is thought that abnormal red blood cells in sickle cell disease contain too little DHA in their cell membrane, and too much of another type of fatty acid, called omega-6. This imbalance is believed to cause inflammation and to contribute to sickle cells sticking together and causing vaso-occlusive crises. The medicine is thought to help re-balance the fatty acid composition of the red blood cells' membrane. This is expected to reduce the symptoms of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine 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 the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 February 2018 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.