EU/3/15/1508

On 19 June 2015, orphan designation (EU/3/15/1508) was granted by the European Commission to Ultragenyx UK Limited, United Kingdom, for triheptanoin for the treatment of very long-chain acyl-CoA dehydrogenase deficiency.

What is very long-chain acyl-CoA dehydrogenase deficiency?

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disease caused by the lack of an enzyme called VLCAD. VLCAD is one of the enzymes needed by the mitochondria (the energy-producing components within cells) to break down certain long fatty acids in order to generate energy. If this enzyme is not present, cells cannot function normally, causing a wide range of signs and symptoms including tiredness, hypoglycaemia (low blood sugar levels), muscle wasting and damage to the heart.

The condition is chronically debilitating and life threatening, particularly as it causes damage to the heart.

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

At the time of designation, VLCAD deficiency affected less than 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 21,000 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).

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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 orphan designation, no satisfactory method had been authorised in the European Union for the treatment of VLCAD deficiency. Treatment of patients primarily involved restriction of dietary fat to less than 30% of the total calories and the substitution of long-chain fatty acids with medium-chain fatty acids. However, these dietary regimens were of unproven value or only partially successful.

How is this medicine expected to work?

Triheptanoin is a synthetic (artificially produced) fat, which is broken down in the liver into substances that can be used by cells to generate energy without the need for VLCAD. By bypassing the need for VLCAD, this medicine is expected to restore the generation of energy and ultimately improve the overall outcome of patients with VLCAD deficiency.

What is the stage of development of this medicine?

The effects of triheptanoin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with triheptanoin in patients with VLCAD deficiency were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for VLCAD deficiency. Orphan designation of triheptanoin had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 May 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.

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