EU/3/11/912: Orphan designation for the prevention of graft loss in pancreatic islet transplantation

Pancreatic islets are clusters of cells (beta cells) within the pancreas which produce insulin. Pancreatic islet transplantation can be used to treat patients with type I diabetes that is difficult to control.

Graft rejection occurs when the recipient's body rejects the transplanted pancreatic islets (the 'graft'). It is caused by the patient's immune system (the body's natural defenses) recognising the transplanted cells as 'foreign' and reacting against them. This results in inflammation and damage to the graft.

Graft rejection in pancreatic islet transplantation is long-term debilitating because it can lead to the progressive loss of beta cells which can result in failure to cure type I diabetes.

At the time of designation, graft rejection in pancreatic islet transplantation affected less than 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 1,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 507,700,000 (Eurostat 2011).

At the time of designation, no satisfactory methods were authorised in the EU for the prevention of graft loss in pancreatic islet transplantation.

Reparixin blocks the activity of a chemokine called CXCL8. Chemokines are proteins produced by certain cells that act as a chemical signal to attract other cells. CXCL8 is produced by cells of the immune system when they recognise the pancreatic islet graft as foreign. It is an important factor in the graft rejection process, as it sends a signal to other immune cells to move to the site of the graft in order to produce an immune response.

Reparixin is expected to work by attaching to the receptors on the surface of immune cells that CXCL8 normally attaches to, thereby blocking its action and preventing graft rejection.

The effects of reparixin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with pancreatic islet transplantation were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for the prevention of graft rejection in pancreatic islet transplantation 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 8 July 2011 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.