EU/3/13/1217: Orphan designation for the treatment of primary sclerosing cholangitis

Primary sclerosing cholangitis is a disease in which there is long-term inflammation and scarring (fibrosis) of the small bile ducts in the liver. These ducts transport fluid called bile from the liver towards the intestines, where it is used to help digest fats. 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 liver cirrhosis (scarring of the liver) and liver failure, and may increase the risk of liver cancer.

At the time of designation, primary sclerosing cholangitis affected not more than 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 15,000 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).

* 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).

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

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with primary sclerosing cholangitis because experimental studies show its effectiveness in reducing excess bile acids and liver damage. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is expected to reduce the amount of bile acid in the liver. It is expected to do so by interfering with the process by which most bile acids in the intestines are recovered and delivered back to the liver through the blood.

This medicine is thought to act locally on the intestines, blocking certain channels called ileal bile acid transporters through which the bile acids leave the intestine to reach the blood vessels that carry them back to the liver. By blocking these channels, the medicine is expected to help reduce the amount of bile acids in the liver, thereby reducing the itching and liver damage seen in patients with primary sclerosing cholangitis.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicinal product in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with primary sclerosing cholangitis had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for primary sclerosing cholangitis 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 6 November 2013 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.