EU/3/15/1526: Orphan designation for the treatment of carnitine palmitoyltransferase II deficiency

Carnitine palmitoyltransferase II deficiency is an inherited disease caused by the lack of an enzyme called CPT II. CPT II is one of the enzymes needed by the mitochondria (the energy-producing components within cells) to break down certain fatty acids in order to generate energy. If this enzyme is lacking, cells cannot function normally causing a wide range of signs and symptoms including hypoglycaemia (low blood sugar levels), exercise-induced muscle pain and weakness, and damage to the liver, brain, nerves and heart.

The condition is chronically debilitating and life-threatening, particularly since it causes hypoglycaemia and damage to the nerves and various organs.

At the time of designation, carnitine palmitoyltransferase II deficiency affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 512,900,000 (Eurostat 2015).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of carnitine palmitoyltransferase II deficiency. Treatment of patients primarily involved restriction of dietary fat, as well as increased frequency of food intake to avoid overloading the body with fatty acids. However, these dietary regimens were of unproven value or only partially successful.

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

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, triheptanoin was not authorised anywhere in the EU for carnitine palmitoyltransferase II deficiency. Orphan designation of the medicine 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 18 June 2014 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.