EU/3/20/2319: Orphan designation for the treatment of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an inherited disease. LCHAD is one of the enzymes needed by the mitochondria (the energy-producing components in cells) to break down certain long-chain fatty acids in order to generate energy. If this enzyme is lacking, the long-chain fatty acids build up in cells and the cells cannot function normally, causing a wide range of effects including tiredness, hypoglycaemia (low blood sugar levels), muscle wasting, abnormalities in the retina (the light-sensitive tissue at the back of the eye) 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, LCHAD deficiency affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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).

*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 orphan designation, no satisfactory methods had been authorised in the European Union for the treatment of LCHAD deficiency. Treatment of patients mainly involved changes to the diet, including eating frequently, restriction of dietary fat and the substitution of long-chain fatty acids with medium-chain fatty acids.

The medicine activates a receptor (target) called PPAR delta which leads to an increase in enzymes involved in converting fatty acids to energy. This is expected to improve energy production and reduce build-up of fatty acids and so reduce symptoms of LCHAD deficiency.

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 the medicine in patients with LCHAD deficiency were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of LCHAD deficiency or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 16 July 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.