EU/3/10/843: Orphan designation for the prevention of arteriovenous access failure in haemodialysis patients

Arteriovenous access failure occurs when blood vessels that are used for haemodialysis become blocked. This can happen because of the formation of blood clots and inflammation.

Haemodialysis is a technique used to clear waste products (such as urea) from the blood of patients whose kidneys are not working, since their kidneys are not able to perform this function. Patients undergoing haemodialysis must have two needles inserted into their blood vessels during the procedure, one to draw the blood out, and one to return it. This is generally done into a blood vessel in the arm that has been specially prepared beforehand to provide a good blood flow. If this blood vessel closes as a result of arteriovenous access failure, haemodialysis cannot be carried out effectively.

Arteriovenous access failure is a life-threatening condition because it makes the dialysis less effective and can lead to further damage to the kidneys.

At the time of designation, the number of haemodialysis patients at risk of arteriovenous access failure was estimated to be approximately 1.3 people in 10,000 per year in the European Union (EU). This was equivalent to a total of around 66,000 people per year*, which was considered to be below the ceiling for orphan designation. 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, there were no satisfactory methods authorised in the EU for the prevention of arteriovenous access failure in haemodialysis patients.

This medicine is an advanced therapy that belongs to the group called 'somatic-cell-therapy products'. These are medicines that contain cells or tissues that have been manipulated to change their biological characteristics so that they can be used to cure, diagnose or prevent a disease.

The medicine is made up of cells from the lining of the aorta (the large blood vessel that carries blood out of the heart) that have been grown in a laboratory and then attached to a spongy matrix. It is intended to be used as a cell transplant.

In the prevention of arteriovenous access failure in haemodialysis patients, the medicine is expected to be applied to the surface of the blood vessels that are to be used for haemodialysis. The matrix is then expected to dissolve and release the aortic cells to be incorporated into the lining of the blood vessel. This is expected to make the lining less likely to become damaged or blocked, and unable to be used for haemodialysis.

The effects of allogeneic aortic endothelial cells cultured in a porcine gelatin matrix have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in haemodialysis patients at risk of arteriovenous access failure had finished and additional studies were planned.

At the time of submission, the medicine was not authorised anywhere in the EU for the prevention of arteriovenous access failure in haemodialysis patients. Orphan designation had been granted in the United States for the prevention of arteriovenous fistula or arteriovenous graft failure in patients with end-stage renal disease receiving haemodialysis or preparing for haemodialysis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 December 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.