EU/3/10/779: Orphan designation for the treatment of familial adenomatous polyposis (FAP)

Familial adenomatous polyposis (FAP) is a hereditary disease in which numerous polyps (growths) form in the gut, mainly in the large intestine. The polyps usually start to develop in late childhood and their number varies from hundreds to thousands. Patients with FAP may have blood in the stools, diarrhoea or constipation, abdominal pain (stomach ache) or weight loss with no obvious cause.

FAP is a long-term debilitating disease that may be life threatening because there is a high risk of it developing into cancer of the large intestine if it is not treated, and can cause problems outside the gut including stomach problems and other types of cancer.

At the time of designation, FAP affected approximately 0.2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 10,000 people, and is below the threshold 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

At the time of designation, celecoxib was authorised in the EU for the treatment of FAP in addition to surgery (to remove the polyps) and endoscopic monitoring (to check if polyps are developing using an endoscope, a thin tube that allows a doctor to look inside the gut).

The sponsor has provided sufficient information to show that eflornithine might be of significant benefit for patients with FAP because early studies indicate that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Eflornithine works by blocking the action of an enzyme called ornithine decarboxylase, which is involved in stimulating cells to grow. In patients with FAP, polyps form because ornithine decarboxylase is overactivated. By blocking this enzyme, eflornithine is expected to slow down the formation of polyps. This medicine is to be available as tablets and as a powder to be taken by mouth.

The effects of eflornithine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with eflornithine in patients with FAP were planned.

At the time of submission, eflornithine cream was authorised for the treatment of facial hirsutism in women (excessive growth of coarse hair on the face) in the EU as well as in several countries worldwide.

At the time of submission, eflornithine was not authorised anywhere in the EU for FAP. Orphan designation of eflornithine had been previously granted for FAP in the EU, but this designation had been later withdrawn by the sponsor.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2010 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.