EU/3/13/1204

On 13 November 2013, orphan designation (EU/3/13/1204) was granted by the European Commission to S-Cubed Limited, United Kingdom, for sirolimus for the prevention of arteriovenous access dysfunction in patients undergoing surgical creation of an arteriovenous access for haemodialysis.

What is arteriovenous access dysfunction?

Arteriovenous access dysfunction occurs when blood vessels that are used for haemodialysis become blocked. Haemodialysis is a technique used to clear waste products (such as urea) from the blood of patients whose kidneys are not working properly, since their kidneys are not able to perform this function.

Patients undergoing haemodialysis usually have two needles inserted into a blood vessel in the arm, one to draw the blood out, and one to return the purified blood back to the patient. This blood vessel is surgically prepared beforehand to allow a good blood flow. However, following the surgery a narrowing can develop which can block the access to the blood vessels. If the narrowing becomes severe, the access closes and haemodialysis can no longer be carried out effectively.

Arteriovenous access dysfunction is a long-term debilitating and potentially life-threatening condition because it makes the dialysis less effective and can lead to further damage to the kidneys.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients undergoing haemodialysis at risk of arteriovenous access dysfunction was estimated to be between 2.9 and 4.4 in 10,000 people in the European Union (EU). This was equivalent to between 149,000 and 225,000 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).

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*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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, there were no satisfactory methods authorised in the EU for the prevention of arteriovenous access failure in haemodialysis patients. Some patients with arteriovenous access dysfunction were treated with angioplasty (a procedure to unblock blood vessels) to improve access or surgery to create a new access.

How is this medicine expected to work?

This medicine is an implant that contains sirolimus, an immunosuppressant medicine that has been used for several years to prevent organ rejection following a transplant.

For the prevention of arteriovenous access dysfunction, this medicine is expected to be implanted around the blood vessels that have been prepared for haemodialysis. The implant is expected to deliver sirolimus to the walls of the blood vessels where it blocks the action of ‘mammalian target of rapamycin’ (mTOR), a protein involved in the growth of muscle cells within the blood vessel wall. By blocking this process, sirolimus is expected to reduce or prevent the growth of the muscle cells that leads to narrowing and blockage of the blood vessels, helping to keep them open.

What is the stage of development of this medicine?

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients undergoing haemodialysis were completed and additional studies were planned.

At the time of submission, the medicine was not authorised anywhere in the EU for preventing arteriovenous access dysfunction in patients undergoing surgical creation of an arteriovenous access for haemodialysis. Orphan designation of the medicine been granted in the United States for the ‘prevention of arteriovenous (AV) fistula or AV 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 9 October 2013 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.