EU/3/02/127: Orphan designation for the treatment of inborn errors in primary bile acid synthesis

The bile is a fluid that helps to digest fats. Bile is made in the liver, and stored in the gallbladder. Bile contains bile acids and other substances. Most bile acids belong to one of two types. These are called cholic acid and chenodeoxycholic acid. These two acids are known as primary bile acids. Bile acids are essential for digesting certain fats. They are also needed for uptake of certain vitamins and to transport cholesterol. Certain proteins called enzymes can build up bile acids from starting materials in the liver (synthesis). In some cases, however, a person lacks the enzymes needed to build up primary bile acids. The condition may be present at birth when it is inherited via the genes from the parents. The lack of bile acids is a serious and chronically debilitating condition.

At the time of orphan designation, there were no medicinal products specifically authorised in the Community for the treatment of inborn errors in primary-bile-acid synthesis.

At the time of designation, inborn errors in primary-bile-acid synthesis affected approximately 0.06 in 10,000 people in the European Union (EU). This was equivalent to a total of around 2,300 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. At the time of designation, this represented a population of 380,600,000 (Eurostat 2002).

It is expected that the cholic acid contained in the medicinal product can replace some of the missing bile acids.

At the time of submission of the application for orphan designation, clinical evaluation in patients with inborn errors in primary-bile-acid synthesis was ongoing.

At the time of submission, cholic acid was not marketed anywhere worldwide for inborn errors in primary-bile-acid synthesis nor was it designated as orphan medicinal product for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 15 November 2002 recommending the granting of this designation.

Update: Cholic acid (Orphacol) was authorised in the EU on 12 September 2013 for the treatment of inborn errors in primary-bile-acid synthesis due to 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency or Δ4-3-oxosteroid-5β-reductase deficiency in infants, children and adolescents aged one month to 18 years and adults.

• the seriousness of the condition;
• the existence or not of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still-investigational products that are considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.