EU/3/20/2302: Orphan designation for the treatment of carnitine-acylcarnitine translocase deficiency

Carnitine-acylcarnitine translocase deficiency is an inherited disease caused by the lack of an enzyme called carnitine-acylcarnitine translocase (CACT). CACT is one of the enzymes needed by the mitochondria (the energy-producing components within cells) to break down certain fatty acids 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), muscle pain, muscle breakdown leading to kidney damage, increased blood levels of ammonia (a sign of liver damage) and damage to the heart muscle.

The condition is chronically debilitating due to tiredness, hypoglycaemia and muscle damage and symptoms such as damage to the heart can be life-threatening.

At the time of designation, carnitine-acylcarnitine translocase 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of CACT deficiency. Treatment of patients primarily involved avoidance of fasting and following a low-fat, high-carbohydrate diet supplemented 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 CACT. By bypassing the need for CACT, this medicine is expected to restore normal energy generation and ultimately improve the overall outcome of patients with CACT deficiency.

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 CACT deficiency were ongoing.

At the time of submission, triheptanoin was not authorised anywhere in the EU for the treatment of carnitine-acylcarnitine translocase deficiency. Orphan designation of triheptanoin had been granted in the United States for fatty acid oxidation disorders.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 June 2020, 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.