EU/3/01/070: Orphan designation for the treatment of familial adenomatous polyposis (FAP)

Familial adenomatous polyposis (FAP), also known as familial polyposis coli, is a hereditary disease characterised by the progressive appearance of numerous polyps mainly in the large intestine. Polyps develop as early as in childhood. The average number of polyps in FAP patients is around 1,000, but this may vary between 100 and 2,500. Polyps are initially benign but can easily become cancerous. FAP may lead to cancer of the large intestine, and as such is a life-threatening condition.

At the time of designation FAP affected approximately 0.3 to 1 in 10,000 people in the European Union (EU) *. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 11,000-38,000 people.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union. This represents a population of 377,000,000 (Eurostat 2001).

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the European Union for treatment of the condition. Available therapeutic methods consisted of endoscopic surveillance with removal of polyps when required. Prophylactic surgery to remove a part of the large intestine is performed if the polyps are numerous or the polyps are becoming cancerous. The patients also receive genetic counselling as the disease is inherited.

Celecoxib is an anti-inflammatory medicine. Its mode of action has been attributed to the inhibition of prostaglandin synthesis, via inhibition of an enzyme (protein molecules that act as catalysts in the cells biochemical reactions) called cyclooxygenase-2 (COX-2). Prostaglandins are a class of hormone-like (chemical messenger) lipids (fats) present in tissues and bodily fluids. They are involved in processes such as pain, inflammation and kidney function. In FAP, celecoxib is thought to induce cell death, and thus prevent or delay the growth of polyps.

The effects of celecoxib were evaluated in experimental models.

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

At the time of submission of the application for orphan designation, celecoxib was authorised for symptomatic relief in the treatment of osteoarthritis or reumathoid arthritis in Sweden. Celecoxib was not authorised anywhere worldwide for FAP, at the time of submission. Orphan designation of celecoxib was granted in Australia in April 2000 for FAP.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 7 September 2001 a positive opinion recommending the grant of the above mentioned designation.

Update: Celecoxib (Onsenal) has been authorised in the EU since 17 October 2003 for the reduction of the number of adenomatous intestinal polyps in familial adenomatous polyposis (FAP), as an adjunct to surgery and further endoscopic surveillance. The effect of Onsenal-induced reduction of polyp burden on the risk of intestinal cancer has not been demonstrated.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.