EU/3/10/834: Orphan designation for the treatment of acute peripheral arterial occlusion

Acute peripheral arterial occlusion is the sudden blockage of an artery supplying blood to the limbs by a blood clot. The blood clot can form locally because the artery is already narrowed, or it can come from another part of the body, for example after surgery to the heart. Typically, the patient experiences severe pain in the affected limb, which also becomes cold and pale. The local nerves may become severely damaged, leading to loss of sensation and the inability to move the limb. The lack of blood flow in the limb could also lead to tissue damage.

Acute peripheral arterial occlusion is a debilitating disease that may be life threatening, especially because of the irreversible tissue damage. It could also lead to amputation of the affected limb.

At the time of designation, acute peripheral arterial occlusion affected less than 1.7 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 86,000 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, satisfactory methods had been authorised in the EU for the treatment of acute peripheral arterial occlusion. These included medicines that activate a protein called plasminogen into its active form, plasmin, which then breaks down the blood clots. In addition, surgery was used to restore the blood flow and prevent limb loss and disability.

The sponsor has provided sufficient information to show that human plasmin might be of significant benefit for patients with this condition because of its direct action on the blood clot causing the blockage of the arteries compared with the indirect action of existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Plasmin is a protein found naturally in the blood that breaks down blood clots. This medicine is a purified form of human plasmin, prepared from human plasma (the liquid part of the blood), which is expected to be delivered directly into the affected arteries of patients with acute peripheral arterial occlusion using a catheter (a thin sterile tube). When delivered, the medicine is expected to break down the clot, thereby removing the obstruction and relieving the patient's symptoms.

The effects of human plasmin have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with human plasmin in patients with acute peripheral arterial occlusion were ongoing.

At the time of submission, human plasmin was not authorised anywhere in the EU for acute peripheral arterial occlusion. Orphan designation of human plasmin had been granted in the United States of America for acute peripheral arterial occlusion.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 November 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.