EU/3/09/653: Orphan designation for the treatment of atypical haemolytic uraemic syndrome (aHUS)

Haemolytic uraemic syndrome (HUS) is a disorder characterised by haemolysis (destruction of red blood cells), thrombocytopenia (a decrease in the number of platelets, components that help the blood to clot), problems with blood clotting and kidney failure. In contrast to most types of HUS, which occur in children after an infection with gut bacteria, atypical HUS (aHUS) affects both children and adults, and is not caused by an infection. More than half of the cases of aHUS are thought to be caused by inherited (inborn) abnormalities of the complement system, a group of proteins in the blood that help the immune system (the body's natural defence system) to fight infections. In patients with aHUS, the complement system is overactive and damages the cells lining the blood vessels. aHUS can be long term, or can keep coming back (relapsing).

aHUS is a long-lasting and life-threatening disease because of the risk of kidney failure.

At the time of designation, aHUS affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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 504,800,000 (Eurostat 2009).

At the time of designation, only supportive treatments for patients with aHUS were available. Transfusions of red blood cells and platelets are given as needed. Dialysis (a blood clearance technique) may be needed if the disease progresses to kidney failure. Some patients may receive infusion of plasma or a therapy called plasma exchange although its role in this condition is not completely clear. Some patients may need a kidney transplant.

Eculizumab is a medicine that is already authorised in the EU for the treatment of paroxysmal nocturnal haemoglobinuria (PNH), a rare, life-threatening genetic disease that causes the red blood cells to be broken down too quickly. Eculizumab is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found in the body. Eculizumab has been designed to attach to a protein of the complement system called C5.

By blocking the C5 complement protein, eculizumab is expected to block the activation of the complement system in patients with aHUS, stopping it from attacking the cells lining the blood vessels. This may reduce their destruction and improve the symptoms of the disease.

The effects of eculizumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with aHUS were ongoing.

At the time of submission, eculizumab was not authorised anywhere in the EU for aHUS or designated as orphan medicinal product elsewhere for this condition. Orphan designation of eculizumab had been granted in the United States for aHUS.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 June 2009 recommending the granting of this designation.

Update: Eculizumab (Soliris) was authorised in the EU on 24 November 2011 for the treatment of patients with atypical haemolytic uraemic syndrome (aHUS).

• 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 Community) 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.