EU/3/14/1406 - orphan designation for treatment of inborn errors in primary bile acid synthesis

Chenodeoxycholic acid

Overview

On 16 December 2014, orphan designation (EU/3/14/1406) was granted by the European Commission to Sigma-Tau Pharma Ltd, United Kingdom, for chenodeoxycholic acid for the treatment of inborn errors in primary bile acid synthesis.

The sponsorship was transferred to sigma-tau Arzneimittel GmbH, Germany, in May 2015.

Chenodeoxycholic acid has been authorised in the EU as Chenodeoxycholic acid sigma-tau since 10 April 2017.

The name of the product changed to Chenodeoxycholic acid Leadiant in May 2017.

The sponsorship was transferred to Leadiant GmbH, Germany, in June 2017.

What are 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.

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

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 isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/14/1406: Public summary of opinion on orphan designation: Chenodeoxycholic acid for the treatment of inborn errors in primary bile acid synthesis

AdoptedReference Number: EMA/COMP/744266/2014 Rev.1

Key facts

• Active substance:
  Chenodeoxycholic acid
• Medicine name:
  Chenodeoxycholic acid sigma-tau
• Intended use:
  Treatment of inborn errors in primary bile acid synthesis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/14/1406
• Date of designation:
  16/12/2014
• Sponsor:

  Leadiant GmbH; Liebherrstraße 22; 80538 München; Germany; Tel. [phone]; E-mail: [e-mail]

Review of designation

On 16 February 2017, the Committee for Orphan Medicinal Products (COMP) concluded its review of the designation EU/3/14/1406 for Chenodeoxycholic acid sigma-tau (chenodeoxycholic 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 methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with inborn errors in primary bile acid synthesis. The COMP recommended that the orphan designation of the medicine be maintained¹.

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¹ 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 EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.