EU/3/19/2182: Orphan designation for the treatment of primary biliary cholangitis

Primary biliary cholangitis is a disease in which there is long-term damage to the small bile ducts in the liver. These ducts transport fluid called bile from the liver to the intestines, where it helps to digest fats. Because of the damage to the ducts, bile acids, essential components of bile, build up in the liver causing damage to liver tissue and leading to liver cirrhosis (scarring of the liver). Early symptoms of the disease include tiredness and itching. The disease is more common in middle-aged women.

Primary biliary cholangitis is a long-term debilitating and life-threatening disease because it can lead to liver cirrhosis and liver failure, and may increase the risk of liver cancer.

At the time of designation, primary biliary cholangitis affected less than 3.9 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 202,000 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 518,400,000 (Eurostat 2019).

At the time of designation, obeticholic acid and ursodeoxycholic acid were authorised in the EU for the treatment of primary biliary cholangitis, with obeticholic acid being used if ursodeoxycholic acid does not work well enough or the patient cannot take it. In advanced cases, the patient may need liver transplantation.

The sponsor has provided sufficient information to show that elafibranor might be of significant benefit for patients with primary biliary cholangitis. Early studies showed that it may work in patients whose condition does not improve with other treatment and the medicine’s effects were greater than those with obeticholic acid. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is expected to work by attaching to and activating receptors (targets) called 'PPAR receptors', which control the levels of bile acid. By activating PPARs, this medicine is expected to reduce the levels of bile acid, thereby reducing damage of liver tissue that occurs in primary biliary cholangitis.

The effects of elafibranor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with elafibranor in patients with primary biliary cholangitis were ongoing.

At the time of submission, elafibranor was not authorised anywhere in the EU for the treatment of primary biliary cholangitis or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 June 2019, 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.