EU/3/02/127

On 18 December 2002, orphan designation (EU/3/02/127) was granted by the European Commission to Agence Générale des Equipements et produits de santé - Etablissement Pharmaceutique des Hôpitaux de Paris (AGEPS - EPHP), France, for cholic acid for the treatment of inborn errors in primary bile acid synthesis.
The sponsorship was transferred to Laboratoires C.T.R.S., France, in July 2007.

What are the 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.

What are the methods of treatment available?

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

What is the estimated number of patients affected by the condition*?

Based on the information provided by the sponsor and previous knowledge of the Committee, inborn errors in primary bile acid synthesis was considered to affect approximately 0.06 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 2,400 persons.

* Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 377,000,000 (Eurostat 2001) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

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

What is the stage of development of this medicinal product?

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.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 15 November 2002 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• the seriousness of the condition, 
• the existence or not of alternative methods of diagnosis, prevention or treatment and 
• 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, which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.