EU/3/14/1257: Orphan designation for the treatment of recombination-activating gene 1 deficient severe combined immunodeficiency

Recombination-activating gene 1 (RAG1) deficient severe combined immunodeficiency (SCID) is an inherited disorder where the patient is unable to fight infections due to the lack of a type of white blood cells called lymphocytes.

It is caused by defects in the gene called RAG1, which makes a protein essential for the development of lymphocytes. Patients with this defect do not produce enough lymphocytes to fight infections and are highly susceptible to bacterial, fungal and viral infections. The main symptoms usually occur in the first six months of life, and include pneumonia, diarrhoea and a failure to grow and develop normally.

RAG1-deficient SCID is a long-term debilitating and life-threatening condition due to repeated and long-lasting infections which can lead to various health problems in the longer term, including developmental disorders, hearing loss, skeletal dysplasia (dwarfism) and liver and kidney problems.

At the time of designation, RAG1-deficient SCID affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 511,100,000 (Eurostat 2014).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of RAG1-deficient SCID. In some patients, allogeneic haematopoietic (blood) stem-cell transplantation was used. This is a complex procedure whereby the patient receives stem cells from a matched donor to help restore the bone marrow.

This medicine is made up of immature bone marrow cells (called CD34+ cells) that are taken from the patient. These cells are able to develop into different types of blood and immune cells. To make this medicine, the CD34+ cells are modified by a virus that contains a normal form of the RAG1 gene, so that this gene is carried into the cells. When these modified cells are transplanted back into the patient, they are expected to grow and be able to produce the lymphocytes which are lacking in patients with RAG1-deficient SCID, and thereby help to relieve the symptoms of the disease.

The type of virus used in this medicine ('lentivirus') is modified in order not to cause disease in humans.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with RAG1-deficient SCID had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for RAG1-deficient SCID or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 February 2014 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.