EU/3/15/1584

On 14 December 2015, orphan designation (EU/3/15/1584) was granted by the European Commission to Diamond BioPharm Limited, United Kingdom, for variant of recombinant human fibroblast growth factor 19 for the treatment of primary sclerosing cholangitis.

What is primary sclerosing cholangitis?

Primary sclerosing 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 towards the intestines, where it is used to help 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 men.

Primary sclerosing cholangitis is a long-term debilitating and life-threatening disease because, when the disease progresses, it may lead to liver cirrhosis 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 approximately 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 82,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 512,900,000 (Eurostat 2015).

What treatments are available?

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 early studies in experimental models show that it might reduce damage to the bile ducts. 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?

Fibroblast growth factor 19 is a protein that controls the production of bile acids. This medicine contains a protein very similar to fibroblast growth factor 19 and is expected to work in the body in a similar way to human fibroblast growth factor 19. When given to the patient, the medicine is expected to decrease the production of bile acids, thereby preventing further damage to the liver and reducing the symptoms of primary sclerosing cholangitis.

The protein in this medicine is made by a method known as ‘recombinant DNA technology’: it is made by bacteria, into which a gene (DNA) has been introduced, that makes them able to produce it.

What is the stage of development of this medicine?

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine in patients with primary sclerosing cholangitis was planned.

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 12 November 2015 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.