EU/3/18/1994: Orphan designation for the treatment of biliary tract cancer

Biliary tract cancer is cancer of the bile ducts and gallbladder. These are parts of the digestive system that transport and store bile, a fluid which is produced by the liver and released into the intestines after a meal to help digest fats. The cancer is characterised by various features such as abnormal liver function tests, pain in the belly, yellowish discoloration of the skin and weight loss.

Biliary tract cancer is a long-term debilitating and life-threatening disease due to liver failure and problems caused when the cancer blocks the bile ducts.

At the time of designation, biliary tract cancer affected approximately 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 67,000 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 517,400,000 (Eurostat 2018).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of biliary tract cancer. Some patients with early disease could undergo surgery to remove the cancer. Other treatments included chemotherapy (medicines to treat cancer).

Some patients with biliary tract cancer have a fault in a gene called IDH1, which causes production of an abnormal IDH1 protein. The abnormal protein makes a substance, 2-hydroxyglutarate, that causes cells to become cancerous. Ivosidenib is expected to block the activity of the abnormal IDH1 protein and so reduces production of 2-hydroxyglutarate, thereby preventing formation of cancer cells.

The effects of ivosidenib have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with ivosidenib in patients with biliary tract cancer were ongoing.

At the time of submission, ivosidenib was not authorised anywhere in the EU for biliary tract cancer 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 15 February 2018 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.