EU/3/15/1581 - orphan designation for treatment of pyruvate dehydrogenase complex deficiency
Sodium phenylbutyrate
OrphanHuman
Overview
On 11 November 2015, orphan designation (EU/5/15/1581) was granted by the European Commission to Fondazione Telethon, Italy, for sodium phenylbutyrate for the treatment of pyruvate dehydrogenase complex deficiency.
Pyruvate dehydrogenase complex deficiency is an inborn disease caused by a lack of certain enzymes in mitochondria (the energy producing components of cells).
Without sufficient amounts of these enzymes (known collectively as the pyruvate dehydrogenase complex), chemical reactions for obtaining energy from food cannot take place and instead other reactions occur that produce lactic acid.
A build-up of lactic acid is a key feature of the condition, and babies with the condition suffer fast breathing, tiredness and poor feeding. Neurological symptoms also start early in life and worsen over time; these symptoms can include poor movement and muscle tone, seizures and slow development of mental ability.
Pyruvate dehydrogenase complex deficiency is debilitating in the long-term and life threatening due to the high levels of lactic acid and the progressive neurological problems.
At the time of designation, pyruvate dehydrogenase complex deficiency 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 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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).
At the time of designation, no satisfactory methods were authorised in the EU for treating pyruvate dehydrogenase complex deficiency.
Sodium phenylbutyrate is expected to work by blocking a group of enzymes called PDKs. Normally PDKs reduce the activity of the pyruvate dehydrogenase complex. By blocking PDKs, sodium phenylbutyrate is expected to increase the activity of the pyruvate dehydrogenase complex, thereby helping to improve patients' symptoms and to slow down the progression of the disease.
The effects of sodium phenylbutyrate 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 pyruvate dehydrogenase complex deficiency had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for pyruvate dehydrogenase complex deficiency 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 8 October 2015 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
- Sodium phenylbutyrate
- Intended use
- Treatment of pyruvate dehydrogenase complex deficiency
- Orphan designation status
- Positive
- EU designation number
- EU/3/15/1581
- Date of designation
- Sponsor
Fondazione Telethon Ets
Via Varese 16 B
00185 Rome
RM
Italy
E-mail: regulatory@telethon.it
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
Update history
| Date | Update |
|---|---|
| November 2022 | The sponsor's name was changed from Fondazione Telethon to Fondazione Telethon Ets in November 2022. |
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: