On 22 August 2014, orphan designation (EU/3/14/1326) was granted by the European Commission to Vall d'Hebron Institute of Research, Spain, for vector based on an adeno-associated virus serotype 2 backbone, pseudo-serotyped with a type 8 capsid, which carries the coding sequence of the human TYMP gene under the control of the human thyroxine binding globulin promoter for the treatment of mitochondrial neurogastrointestinal encephalomyopathy.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an inherited disease caused by mutations (defects) in the TYMP gene, which is responsible for the production of an enzyme called 'thymidine phosphorylase'. This enzyme controls the amount of certain compounds in the cells, such as thymidine.
Patients with the disease do not have enough of the thymidine phosphorylase enzyme and therefore are unable to break down thymidine, causing it to build up in the cells, where it damages the DNA contained in mitochondria, which are important organelles of the cell. Damaged mitochondrial DNA leads to the symptoms of the disease, although the exact way in which this happens is not clear.
The disease affects many parts of the body, particularly the digestive system, where it causes problems such as nausea (feeling sick), stomach ache, bloating, diarrhoea and weight loss, and the nervous system, where it causes symptoms such as weakness, numbness and tingling sensations mostly in the hands and feet. Symptoms can appear at any time from birth but usually start during the second decade of life, and worsen with time.
MNGIE is a debilitating disease that is long lasting and life threatening due to its effects on the gut and on the nervous system.
At the time of designation, MNGIE affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).
At the time of designation, no satisfactory methods were authorised in the EU for the treatment of MNGIE. Patients were given treatments to help alleviate their symptoms and genetic counselling (discussion of the risks of passing the condition on to children). In some patients, allogeneic stem-cell transplantation was used. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.
This medicine is made of a virus that contains a normal copy of the TYMP gene, which produces the thymidine phosphorylase enzyme, attached to a liver-specific promoter (a genetic 'switch' which only allows it to work inside liver cells). When the medicine is given to the patient, the virus is expected to carry the TYMP gene into the liver cells where it produces thymidine phosphorylase. It is expected that thymidine phosphorylase will then break down the thymidine that enters the liver via the bloodstream, thus avoiding its build-up in cells and improving the symptoms of the disease.
The type of virus used in this medicine ('adeno-associated virus') does not cause disease in humans.
The effects of the medicine 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 MNGIE had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for MNGIE 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 10 July 2014 recommending the granting of this designation.
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.
Vall d'Hebron Institute of Research
Pg. Vall d'Hebron 119-129
08035 Barcelona
Spain
Tel. +34 934 894054
Fax +34 932 746763
E-mail: ramon.marti@vhir.org
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: