EU/3/10/753 - orphan designation for treatment of primary biliary cirrhosis

6alpha-ethyl-chenodeoxycholic acid

Overview

On 27 July 2010, orphan designation (EU/3/10/753) was granted by the European Commission to Intercept Pharma, Italy, for 6alpha-ethyl-chenodeoxycholic acid (also known as obeticholic acid) for treatment of primary biliary cirrhosis.

6alpha-ethyl-chenodeoxycholic acid has been authorised in the EU as Ocaliva since 12 December 2016.

What is primary biliary cirrhosis?

Primary biliary cirrhosis is a disease in which there is gradual destruction of the small bile ducts in the liver. These ducts transport a fluid called bile towards the intestines, where it is used to help digest fats. As a result of the damage to the ducts, bile builds up in the liver and damages the liver tissue. Early symptoms of the disease include tiredness and pruritus (itching).

Primary biliary cirrhosis is ten times more common in women than in men. It is a long-term debilitating and life-threatening disease because, when the disease progresses, it may lead to liver cirrhosis (scarring of the liver) and liver failure (an inability of the liver to work properly).

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

At the time of designation, primary biliary cirrhosis affected not more than 3.9 in 10,000 people in the European Union (EU)*. This is equivalent to a total of not more than 182,000 people, and is below the threshold 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).

What treatments are available?

At the time of designation, ursodeoxycholic acid was authorised in most EU countries for the treatment of primary biliary cirrhosis. Although this medicine can help to improve the flow of bile, about a third of patients with primary biliary cirrhosis do not respond to it. In advanced cases, the patient may need a liver transplant.

The sponsor has provided sufficient information to show that 6alpha-ethyl-chenodeoxycholic acid might be of significant benefit for patients with primary biliary cirrhosis because it might improve the treatment of patients with this condition, particularly patients who do not respond to the existing treatment. 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?

6alpha-ethyl-chenodeoxycholic acid is a natural bile acid that has been chemically modified to make it more active. It is expected to work mainly by activating the farnesoid X receptor (FXR), which controls the production of bile. By activating this receptor, this medicine is expected to reduce the production of bile in the liver, preventing it building up and damaging the liver tissue.

What is the stage of development of this medicine?

The effects of 6alpha-ethyl-chenodeoxycholic acid have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with 6alpha-ethyl-chenodeoxycholic acid in patients with primary biliary cirrhosis were ongoing.

At the time of submission, 6alpha-ethyl-chenodeoxycholic acid was not authorised anywhere in the EU for primary biliary cirrhosis. Orphan designation of 6alpha-ethyl-chenodeoxycholic acid had been granted in the United States of America for primary biliary cirrhosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 April 2010 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/3/10/753: Public summary of opinion on orphan designation 6alpha-ethyl-chenodeoxycholic acid for treatment of primary biliary cirrhosis

AdoptedReference Number: EMA/COMP/235947/2010

Key facts

• Active substance:
  6alpha-ethyl-chenodeoxycholic acid
• Medicine name:
  Ocaliva
• Intended use:
  Treatment of primary biliary cirrhosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/10/753
• Date of designation:
  27/07/2010
• Sponsor:

  Advanz Pharma Limited; Suite 17; Northwood House; Northwood Crescent; Northwood; Dublin 9; Co. Dublin; D09 V504; Ireland; E-mail: [e-mail]

Review of designation

On 14 October 2016, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/10/753 for Ocaliva (obeticholic acid¹) as an orphan medicinal product for the treatment of primary biliary cirrhosis. 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 primary biliary cirrhosis. The COMP recommended that the orphan designation of the medicine be maintained².

---

¹Previously known as 6alpha-ethyl-chenodeoxycholic acid.

²The 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.