EU/3/19/2242 - orphan designation for treatment of sickle cell disease

autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene

Overview

On 9 January 2020, orphan designation EU/3/19/2242 was granted by the European Commission to Vertex Pharmaceuticals (Ireland) Limited, Ireland, for autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene (CTX001) for the treatment of sickle cell disease.

The sponsor’s address was updated in January 2022.

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 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 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 67,000 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).

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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 518,400,000 (Eurostat 2019).

What treatments are available?

At the time of designation, the only medicine authorised in the EU to treat sickle cell disease was hydroxycarbamide, also known as hydroxyurea. The main treatment 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. This is because early studies demonstrate that a single treatment resulted in consistent production of foetal haemoglobin over at least 4 months, which reduced the need for other treatments such as transfusions. 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?

The medicine is made up of immature bone marrow (haematopoietic) cells that are taken from the patient. These cells are modified to make them produce gamma-globin, one of the components of foetal haemoglobin, which is normally not produced beyond one year after birth. When they are given back to the patient, the modified cells are expected to produce gamma-globin which will in turn lead to the production of foetal haemoglobin. This type of haemoglobin is expected to decrease the abnormal sickling of red blood cells and reduce anaemia.

The modification of the cells is made using CRISPR-Cas9, an enzyme combined with a small piece of genetic material (RNA) that is able to edit a specific gene. In this medicine, CRISPR-Cas9 creates defects in a gene for a protein called BCL11A which normally stops the production of gamma-globin. These defects prevent the production of BCL11A and allow gamma-globin to be produced.

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, 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 or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 5 December 2019, 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/3/19/2242: Public summary of opinion on orphan designation for autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene for the treatment of sickle cell disease

AdoptedReference Number: EMADOC-628903358-1827

Key facts

• Active substance:
  autologous CD34+ hematopoietic stem cells with a CRISPR-edited erythroid enhancer region of the BCL11A gene
• Intended use:
  Treatment of sickle cell disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/19/2242
• Date of designation:
  09/01/2020
• Sponsor:

  Vertex Pharmaceuticals (Ireland) Limited; Unit 49; Northwood Court; Block F2 Santry; Dublin 9; Ireland; E-mail: [e-mail]