EU/3/15/1581 - orphan designation for treatment of pyruvate dehydrogenase complex deficiency

sodium phenylbutyrate

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.

What is 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.

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

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 is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for treating pyruvate dehydrogenase complex deficiency.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

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.

EU/3/15/1581: Public summary of opinion on orphan designation: Sodium phenylbutyrate for the treatment of pyruvate dehydrogenase complex deficiency

Adopted Reference Number: EMA/COMP/699685/2015

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:
  11/11/2015
• Sponsor:

  Fondazione Telethon Ets;

Review of designation

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