EU/3/20/2335: 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, changing 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. Obstruction of blood vessels can cause episodes of severe pain (vaso-occlusive crises) and long-term damage to organs. Patients with the disease suffer 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 less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 104,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide, also known as hydroxyurea. Another treatment often relied upon for sickle cell disease was blood transfusion. In some cases, haematopoietic (blood) stem cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow) was used 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 have found that haemoglobin levels increased in patients when the medicine was used in combination with hydroxycarbamide. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is expected to stimulate the activity of an enzyme found in red blood cells, PKR. This is expected to reduce the rigid change in shape of red blood cells and prolong their lifespan, thus reducing anaemia and the number of vaso-occlusive crises.

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 the treatment of sickle cell disease. Orphan designation for the medicine had been granted in the United States for sickle cell disease.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 10 September 2020, 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.