EU/3/13/1228

On 21 March 2014, orphan designation (EU/3/13/1228) was granted by the European Commission to Intercept Italia S.R.L., Italy, for obeticholic acid for the treatment of primary sclerosing cholangitis.

The sponsorship was transferred to Intercept Pharma Ltd, United Kingdom, in June 2016.

What is primary sclerosing cholangitis?

Primary sclerosing cholangitis is a condition in which there is long-term inflammation and scarring (fibrosis) of the bile ducts in the liver. These ducts are tubes through which bile, a liquid produced by the liver to help digest fats, flows to the intestine. As a result of the damage to the ducts, bile acids, essential components of bile, build up in the liver and damage the liver tissue. Early symptoms of the disease include tiredness and itching. The disease is more common in middle-aged men.

Primary sclerosing cholangitis is a long-term debilitating and life-threatening disease because, when the disease progresses, it may lead to portal hypertension (high blood pressure in the vessels connecting the liver and the gut), liver cirrhosis (scarring of the liver) and liver failure, and may increase the risk of liver cancer.

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

At the time of designation, primary sclerosing cholangitis affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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).

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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 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, ursodeoxycholic acid was authorised in some EU countries to treat primary sclerosing cholangitis. In advanced cases, the patient may need a liver transplant.

The sponsor has provided sufficient information to show that obeticholic acid might be of significant benefit for patients with the condition because early preclinical studies show the medicine may have a beneficial effect on liver scarring and in reducing portal hypertension. 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?

Obeticholic acid is a modified form of a bile acid. It is expected to work mainly by activating a receptor known as farnesoid X receptor (FXR), which controls the production of bile acid. By activating this receptor, this medicine is expected to reduce the production of bile acid in the liver, preventing it from building up and damaging the liver tissue.

What is the stage of development of this medicine?

The effects of obeticholic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with obeticholic acid in patients with primary sclerosing cholangitis had been started.

At the time of submission, the product was not authorised anywhere in the EU for primary sclerosing cholangitis. Orphan designation had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 December 2013 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.