EU/3/14/1263 - orphan designation for the treatment of sickle cell disease

Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene

Overview

Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2021 on request of the sponsor.

On 29 April 2014, orphan designation (EU/3/14/1263) was granted by the European Commission to bluebird bio France SARL, France, for autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene for the treatment of sickle cell disease.

The sponsorship was transferred first to bluebird bio (Germany) GmbH, Germany, in July 2018 and subsequently to bluebird bio (Netherlands) B.V., Netherlands, in December 2019.

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. 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, the disease causes severe pain and damage to these 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 approximately 2.16 in 10,000 people in the European Union (EU). This was equivalent to a total of around 110,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide. The main treatment for sickle cell disease was blood transfusion. 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 treatments and early studies show that it might provide an alternative for patients who are intolerant or do not respond to hydroxycarbamide. 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?

This medicine is made up of 'haematopoietic stem cells' that are taken from the patient. Haematopoietic stem cells are cells that can develop into different types of blood cell. To make this medicine, the patient's stem cells are modified in the laboratory by a virus that carries healthy copies of the gene that is defective in patients with sickle cell disease (the beta-globin gene) into the cells. When these modified cells are transplanted back into the patient, they are expected to develop into healthy red blood cells containing normal haemoglobin, and thereby avoid the need for blood transfusion, bone marrow transplantation or other treatments.

The type of virus used in this medicine (a 'lentivirus') is modified so that it does not cause disease in humans.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, preliminary clinical trials with the medicine in patients with sickle cell disease had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of sickle cell disease. Orphan designation of the medicine had been granted in the United States for this condition, and in the EU and the United States for the treatment of beta-thalassaemia intermedia and major.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 March 2014 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.

EU/3/14/1263: Public summary of opinion on orphan designation: Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene for the treatment of sickle cell dise...

AdoptedReference Number: EMA/COMP/172803/2014 Rev.1

Key facts

• Active substance:
  Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human beta A-T87Q-globin gene
• Intended use:
  The treatment of sickle cell disease
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/14/1263
• Date of designation:
  29/04/2014
• Sponsor:

  bluebird bio (Netherlands) B.V.; Stadsplateau 7; Utrecht; 3521 AZ; Netherlands; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.