EU/3/10/753: Orphan designation for the treatment of 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).

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).

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.

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.

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.

• 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.