EU/3/09/720: Orphan designation for the treatment of Stargardt's disease

Stargardt's disease is a genetic disorder of the eye that leads to the gradual loss of sight. It is caused by abnormalities in a gene called ABCA4. The ABCA4 gene is responsible for the production of a protein called ABCR, which controls the movement of substances into and out of cells in the retina (the light-sensitive surface at the back of the eye). In patients with Stargardt's disease, ABCR does not work properly. This causes deposits to build up inside the retina cells, which become damaged and eventually die.

Stargardt's disease is a long-term debilitating disease because it leads to the patient's sight getting worse and eventually to blindness.

At the time of designation, Stargardt's disease affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 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 submission of the application for orphan designation, no satisfactory methods were authorised in the EU for the treatment of Stargardt's disease. Patients with the disease were usually given physical aids such as sunglasses to reduce the rate of damage to the retina, or spectacles, magnifiers or telescopes to help them see during the early stages of the disease. Laser treatment can help to stabilise the loss of vision in some patients. Patients also often have genetic counselling (discussion of the risks of passing the condition on to children).

Lentiviral vector containing the human ABCA4 gene is an advanced therapy medicine that belongs to the group called 'gene therapy products'. These are medicines that work by delivering genes into the body. The medicine is made up of a virus that contains the human ABCA4 gene. The virus is used to carry the ABCA4 gene into the cells of the retina. These cells can then start to produce normal ABCR protein to replace the defective protein. When it is injected into the eye, the medicine is expected to relieve the symptoms of the disease and prevent the loss of sight. The type of virus used in this medicine (lentivirus) is modified so that it does not cause disease in humans.

At the time of submission of the application for orphan designation, the evaluation of the effects of lentiviral vector containing the human ABCA4 gene in experimental models was ongoing.

At the time of submission, no clinical trials with the designated product in patients with Stargardt's disease had been started.

At the time of submission, lentiviral vector containing the human ABCA4 gene was not authorised anywhere in the EU for Stargardt's disease 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 3 December 2009 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.