EU/3/13/1134: Orphan designation for the treatment of adenosine-deaminase-deficient severe combined immunodeficiency

Adenosine-deaminase-deficient severe combined immunodeficiency (SCID) is an inherited disorder where the patients are unable to fight infections due to defective white blood cells called lymphocytes.

It is caused by a defect in the gene for adenosine deaminase, an enzyme that helps cells to clear waste products and is particularly important for cells such as lymphocytes which multiply rapidly and produce more waste. As a consequence, waste accumulates in the lymphocytes and damages them. Patients therefore do not have enough white blood cells 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.

Adenosine-deaminase-deficient SCID is a long-term debilitating and life-threatening condition due to repeated and long-lasting infections. If left untreated the disease is usually fatal in the first two years of life, while it 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, adenosine-deaminase-deficient SCID affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).

At the time of designation, no satisfactory methods were authorised in the European Union for the treatment of adenosine-deaminase-deficient SCID. In some patients, allogeneic haematopoietic (blood) stem-cell transplantation was used. This is a complex procedure where 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 the gene for the adenosine deaminase enzyme, so that this gene is carried into the cells. When these modified cells are transplanted back into the patient, they are expected to populate the bone marrow and produce healthy blood and immune cells that produce the adenosine deaminase enzyme, which is lacking in patients with adenosine-deaminase-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.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with adenosine deaminase-deficient SCID had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for adenosine-deaminase-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 17 April 2013 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.