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Orphan designation

On 13 May 2011, orphan designation (EU/3/11/860) was granted by the European Commission to Institut de la Vision, France, for adeno-associated viral vector containing the human NADH-dehydrogenase-4 gene for treatment of Leber's hereditary optic neuropathy.

The sponsorship was transferred to Gensight-Biologics, France, in September 2013.

What is Leber's hereditary optic neuropathy?

Leber's hereditary optic neuropathy is a hereditary disease of the optic nerve, the nerve at the back of the eye that transmits signals to the brain. The disease is due to mutations in the mitochondrial genes that render the mitochondria, the energy-producing components within cells, unable to work properly. Patients inherit the mutation from their mothers. While all children of an affected mother carry the mutation, not all are affected by the disease. Those who are affected (about 80% of the sons and half of the daughters) rapidly lose their sight over a period of few months by their mid-twenties. The reason why patients start to lose their sight is unclear, but environmental and lifestyle factors such as smoking or alcohol consumption may play a role.

Leber's hereditary optic neuropathy is a long-term debilitating disease because of the visual loss and development of blindness.

What is the estimated number of patients affected by the condition?

At the time of designation, Leber's hereditary optic neuropathy affected less than 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 51,000 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. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

What treatments are available?

At the time of designation, there were no satisfactory methods authorised in the EU for the treatment of Leber's hereditary optic neuropathy. Patients carrying the genetic mutation were advised to avoid lifestyle factors known to be involved in triggering the onset of blindness, such as smoking and alcohol consumption.

How is this medicine expected to work?

Adeno-associated viral vector containing the human NADH-dehydrogenase-4 gene is a medicine that works by delivering genes into the body. It is made up of a virus that contains the gene for an enzyme called ‘NADH dehydrogenase 4’. Patients who carry the genetic mutation that cause Leber’s hereditary optic neuropathy have mitochondria that cannot function normally as they are not able to produce this enzyme. The medicine is expected to be injected into the optic nerve, where the virus will deliver the gene so that the enzyme can be produced and the mitochondrial function can be improved. This is expected to prevent or slow down the loss of vision.

The type of virus used in this medicine (adeno-associated virus) does not cause disease in humans.

What is the stage of development of this medicine?

The effects of adeno-associated viral vector containing the human NADH-dehydrogenase-4 gene 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 Leber’s hereditary optic neuropathy had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for Leber’s hereditary optic neuropathy 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 9 February 2010 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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.

Key facts

Product details for <p>Adeno-associated viral vector containing the human NADH-dehydrogenase-4 gene</p>
Active substanceAdeno-associated viral vector containing the human NADH-dehydrogenase-4 gene
Medicine Name
Disease/conditionTreatment of Leber's hereditary optic neuropathy
Date of decision13/05/2011
Orphan decision numberEU/3/11/860

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.

Sponsor’s contact details

74 rue du Faubourg St Antoine
75012 Paris
Tel. +33 1762 17220

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.