EU/3/02/127

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Orphan designation

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.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What are 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 were no medicinal products 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*?

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).

How is this medicine expected to work?

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 medicine?

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.

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;
  • 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.

Key facts

Product details for <p>Cholic acid</p>
Active substanceCholic acid
Medicine NameOrphacol
Disease/conditionTreatment of inborn errors of primary-bile-acid synthesis
Date of decision17/12/2002
OutcomePositive
Orphan decision numberEU/3/02/127

Review of designation

During its meeting of 11-12 January 2011, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/02/127 for Orphacol (cholic acid) as an orphan medicinal product for the treatment of inborn errors in primary-bile-acid synthesis. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained*.


*The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the European Union (EU). This means that in the 10 years after its authorisation, similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Orphacol 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’.

This falls within the scope of the product’s designated orphan condition, which is ‘treatment of inborn errors in primary-bile-acid synthesis’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2002. Inborn errors in primary-bile-acid synthesis remain a condition that is debilitating in the long term and life-threatening, particularly due to the development of liver cirrhosis and liver failure.

Prevalence of the condition

The sponsor provided recent data on the prevalence of the orphan condition, inborn errors in primary-bile-acid synthesis, from the scientific literature published since the orphan designation of Orphacol in 2002.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of this condition remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence of inborn errors in primary-bile-acid synthesis was estimated to be between 0.06 and 0.07 people in 10,000. This is equivalent to a total of between 3,000 and 3,500 people in the EU.

Existence of other satisfactory methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no satisfactory treatments were authorised in the EU for patients affected by this condition.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Orphacol still met the criteria for designation as an orphan medicinal product and that the medicine should remain in the Community register of orphan medicinal products.

Related information

Sponsor’s contact details

Laboratoires C.T.R.S.
69 rue d’Aguesseau
92100 Boulogne Billancourt
France
Tel. +33 1 41 22 09 70
Fax +33 1 41 22 02 36

Partients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.