EU/3/05/303: Orphan designation for the treatment of anal fistula

An anal fistula is an abnormal passageway that develops between the rectum (the lower part of the large intestine that stores faeces) and the outside of the body. This results in abnormal discharge of faeces through an opening other than the anus.

Anal fistulae are usually caused by an infection or an abscess (collection of pus) in the anus. They can also result from other diseases that cause long-term inflammation of the bowel. Patients with an anal fistula have constant pain, sometimes accompanied by swelling and irritation of skin around the anus, leakage of pus, diarrhoea and fever.

Anal fistula is a long-term debilitating disease because it can lead to incontinence (a lack of control over the opening of the bowels) and sepsis (blood infection).

At the time of designation, anal fistula affected approximately 1.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 84,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

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. Certain anal fistulas heal spontaneously, however fistula surgery is usually necessary. Fistula surgery involves cutting a small portion of the anal sphincter (a ring of muscle fibers controlling the opening and closing of the anus) to open the tunnel, joining the external and internal opening and converting the tunnel into a groove that will then heal from within outward.

This medicine is made up of 'mesenchymal stem cells' that are extracted from the patient's own adipose (fat) tissue. To make this medicine, the cells are isolated and cultivated using a technique called ex vivo expansion to increase their number. When these cells are injected into the walls of the fistula, they are expected to send signals that reduce the activity of the immune system and inflammation. Once the inflammation in the fistula has subsided, new tissue can start to grow, helping the fistula to heal.

At the time of submission of the application for orphan designation, the evaluation of the effects of human autologous mesenchymal adult stem cells extracted from adipose tissue in experimental models was ongoing.
At the time of submission of the application for orphan designation, clinical trials in patients with anal fistula were ongoing.

Human autologous mesenchymal adult stem cells extracted from adipose tissue was not authorised anywhere worldwide for treatment of anal fistula or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 July 2005 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.