EU/3/05/313: Orphan designation for the treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency

Severe combined immunodeficiency, or SCID, is a group of inherited disorders characterized by little or no body's defence (immune) response due to the total or partial lack of those specilised white cells (lymphocytes) which are normally part of the body's defense system. A form of SCID is caused by a lack of adenosine deaminase (ADA), an enzyme (a protein that speeds up the conversion of certain substances into other substances) which helps the cell to clear the waste products it generates during proliferation. This enzyme is important in every cell of the body but in particular in those cells which proliferate rapidly, like the lymphocytes. As a consequence of the adenosine deaminase (ADA) deficiency, lymphocytes, which proliferate greatly during their maturation, are injured by these accumulation of toxic metabolites. This deficiency usually results in the onset of one or more serious infections within the first few months of life. The symptoms of this type of SCID include an increased susceptibility to a variety of infections, including ear infections, lung infections and diarrhea. Because children with SCID experience multiple infections, they fail to grow and to gain weight as expected. Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is chronically debilitating and life-threatening.

At the time of designation, severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 900 people*, and is below the threshold 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

At the time of submission of the application for the orphan drug designation there were no products authorised in the European Union. Treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency included compatible donor (heterologous) bone-marrow transplantation to replace the defective cells.

The gene coding for the adenosine deaminase enzyme, carried by a so-called “retroviral vector”, is inserted (transfected) into the patient's own progenitor bone marrow cells (so-called CD34+ cells), previously isolated. It is assumed that, once admininistrated back to the patient, these CD34+ cells transfected with the adenosine deaminase gene will be able to produce their own genetic material (nucleosides) in a normal way and thus actively proliferate in order to restore the normal number of functional white blood cells (lymphocytes).

The effects of autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency were ongoing.

Autologous CD34+ cells transfected with retroviral vector containing adenosine deaminase gene was not authorised anywhere worldwide for the treatment of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2005 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 European Union) 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.