EU/3/14/1406: Orphan designation for the treatment of inborn errors in primary bile acid synthesis

Inborn errors in primary bile acid synthesis are a group of diseases in which the liver does not produce ('synthesise') enough 'primary bile acids'. These acids are the main components of the bile, a fluid that helps break down fats in the digestive tract, and include cholic acid and chenodeoxycholic acid. The lack of bile acids is caused by inborn genetic abnormalities.

Patients lacking primary bile acids produce abnormal bile acids instead, which can damage the liver and in some cases, lead to liver failure. Patients may also have neurological problems and problems with absorbing fats and fat-soluble vitamins.

Inborn errors in primary bile acid synthesis are a group of long-term debilitating and life-threatening diseases because they can severely damage the liver and they can cause neurological problems and problems with food absorption.

At the time of designation, inborn errors in primary bile acid synthesis affected not more than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 10,000 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 511,100,000 (Eurostat 2014).

At the time of designation, two cholic acid products, Orphacol and Kolbam (previously Cholic Acid FGK), were authorised in the EU for treating inborn errors in primary bile acid synthesis.

The sponsor has provided sufficient information to show that chenodeoxycholic acid might be of significant benefit for patients with inborn errors in primary bile acid synthesis. This is based on results of studies in the published literature indicating that chenodeoxycholic acid could potentially be more beneficial than currently authorised treatments and that it could prevent worsening of the disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Chenodeoxycholic acid is one of the main primary bile acids produced by the liver. The chenodeoxycholic acid contained in this medicine is expected to replace the patient's missing bile acids and thereby reduce the production of abnormal bile acids and contribute to the normal activity of bile in the digestive system.

Chenodeoxycholic acid is already authorised in the EU for the treatment of gallstones.

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

At the time of submission of the application for orphan designation, no clinical studies in patients with inborn errors in primary bile acid synthesis were planned.

At the time of submission, the medicine was not authorised anywhere in the EU for inborn errors in primary bile acid synthesis 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 13 November 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.