EU/3/11/937 - orphan designation for treatment of Leigh syndrome
Alpha-tocotrienol quinone
OrphanHuman
Overview
On 9 December 2011, orphan designation (EU/3/11/937) was granted by the European Commission to Edison Europe Holding BV, the Netherlands, for alpha-tocotrienol quinone for the treatment of Leigh syndrome.
The sponsorship was transferred to PTC Therapeutics International Limited, Ireland, in November 2019.
Leigh syndrome, also known as subacute necrotising encephalomyelopathy, is an inherited disease of the brain and the nervous system leading to problems such as poor motor function (movement), weakness, lack of muscle tone and difficulty breathing. Symptoms typically start before the age of 12 months.
The disease has many genetic causes, all of which are linked to defects in the mitochondria, the energy-producing components within cells.
Leigh syndrome is debilitating and life threatening due to progressive worsening of nervous system function as well as problems with heart, kidney and hormonal glands.
At the time of designation, Leigh syndrome affected approximately 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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).
No satisfactory methods of treatment were authorised in the EU at the time of designation. Patients received supportive therapy to deal with the symptoms such as mechanical support with breathing, vitamins and supplements.
Alpha-tocotrienol quinone is manufactured from vitamin E and is given by mouth. It is expected to enter cells of the central nervous system, where it will increase the levels of a substance called glutathione. Low levels of glutathione are seen in patients with Leigh syndrome and are thought to be linked to the development of the symptoms of the disease.
The effects of alpha-tocotrienol quinone have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with alpha-tocotrienol quinone in patients with Leigh syndrome were ongoing.
At the time of submission, alpha-tocotrienol quinone was not authorised anywhere in the EU for Leigh syndrome. Orphan designation of alpha-tocotrienol quinone had been granted in the United States of America for the treatment of inherited mitochondrial respiratory chain diseases.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2011 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.
Key facts
- Active substance
- Alpha-tocotrienol quinone
- Intended use
- Treatment of Leigh syndrome
- Orphan designation status
- Positive
- EU designation number
- EU/3/11/937
- Date of designation
- Sponsor
PTC Therapeutics International Limited
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: