EU/3/10/822 : Orphan designation for the treatment of Fanconi anaemia type A

Fanconi anaemia is an inherited genetic disorder. 'Type A' is the most common form of Fanconi anaemia. Patients with Fanconi anaemia type A have a defect in the Fanconi-A (FANCA) gene normally involved in the recognition and repair of damaged cell DNA. The defect prevents cells from replicating normally. Patients with Fanconi anaemia are generally born with physical malformations, and over the years, they develop a wide range of complications such as bone marrow failure (the body's inability to produce new blood cells) and cancers such as acute myeloid leukaemia (a cancer of the white blood cells). Bone marrow failure normally occurs during childhood.

Fanconi anaemia is a severely debilitating and life-threatening condition because of the bone marrow failure which leads to shortened life expectancy.

At the time of designation, Fanconi anaemia type A affected between 0.01 and 0.05 in 10,000 people in the European Union (EU). This was equivalent to a total of between 500 and 2,500 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. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, while different medicines were authorised to treat specific complications resulting from the disease, there were no satisfactory treatments authorised in the EU for Fanconi anaemia. The only treatment available was allogeneic haematopoietic (blood) stem cell transplantation (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow), but the availability of suitable donors was limited.

Lentiviral vector carrying the FANCA gene is a 'gene therapy product'. This is a medicine that works by delivering genes into the body. The medicine is made up of a virus that contains normal copies of the FANCA gene. Haematopoietic stem cells (cells that can develop into different types of blood cells) are first taken from the patient and then 'infected' with the virus so that the healthy FANCA gene is carried into the cells. These modified cells are transplanted back into the patient where they are expected to start producing healthy blood cells thus altering or halting the disease.

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

The effects of lentiviral vector carrying the FANCA gene have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for Fanconi anaemia type A 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 7 October 2010 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.