EU/3/07/434: Orphan designation for the treatment of Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy is an inherited disease characterised by progressive loss of sight. Patients affected by Leber's hereditary optic neuropathy have mutations in the genetic material of mitochondria. Mitochondria are structures located inside cells, which produce the energy necessary for cells to function. It is thought that the mutations lead to a defective function of the mitochondria in the optic nerve cells and to degeneration of these cells that are needed for vision. Leber's hereditary optic neuropathy is chronically debilitating due to progressive loss of vision.

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 46,000 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 based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition. Patients with Leber's hereditary optic neuropathy usually receive genetic counselling and general support such as information and regular medical follow up.

Mitochondria produce the energy necessary for the cell functioning through a process named “cellular respiration” which requires oxygen and produces energy. During cellular respiration, some toxic forms of oxygen (called oxygen free radicals) can be produced; these must be neutralised by other substances to avoid cellular damage. Idebenone is expected to act as a neutraliser of these toxic forms of oxygen. Thus, idebenone is expected to have an antioxidant effect, and consequently prevent cellular damage.

At the time of submission of the application for orphan designation, the effects of idebenone had been evaluated in experimental models, and clinical trials in patients with Leber's hereditary optic neuropathy were planned.

Idebenone was not authorised anywhere in the world for treatment of Leber's hereditary optic neuropathy 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 10 January 2007 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.