EU/3/12/1015

On 4 July 2012, orphan designation (EU/3/12/1015) was granted by the European Commission to Alexion Europe SAS, France, for eculizumab for the treatment of infection-associated haemolytic uraemic syndrome.

What is infection-associated haemolytic uraemic syndrome?

Haemolytic uraemic syndrome (HUS) is a disorder characterised by three main signs: haemolysis (destruction of red blood cells), thrombocytopenia (a decrease in the number of platelets, components that help the blood to clot) and kidney failure.

The underlying problem in HUS is damage to the cells lining the blood vessels, which causes the destruction of red blood cells passing through the vessels, uses up the platelets in the blood and affects the function of blood vessels in the kidneys.

Infection-associated HUS is thought to be caused by bacteria over-activating part of the immune system called the ‘complement system’. The overactive complement system then causes damage to the cells lining the blood vessels, leading to the development of the signs of the disease. Infection-associated HUS usually occurs in children, and is most often caused by a Shiga-toxin-producing bacterial infection, caught through an infected food source.

Infection-associated HUS is a long-lasting and life-threatening disease mainly because of the risk of kidney failure and neurological complications affecting the brain.

What is the estimated number of patients affected by the condition?

At the time of designation, infection-associated HUS affected less than 0.07 people in 10,000 per year in the European Union (EU)*. This is equivalent to a total of fewer than 4000 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. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, only supportive treatments for patients with infection-associated HUS were available. Transfusions of red blood cells and platelets were given as needed. Dialysis (a blood clearance technique) was used if the disease progressed to kidney failure. Some patients received infusion of plasma or a therapy called plasma exchange although its role in this condition was not completely clear. Some patients needed a kidney transplant. In case of neurological complications such as seizures (fits), anti-epileptic medicines were used.

How is this medicine expected to work?

Eculizumab is a medicine that is already authorised in the EU for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS), two rare, life-threatening genetic diseases that cause the destruction of red blood cells resulting in various medical complications. 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 and block a protein of the complement system called C5.

By attaching to the C5 complement protein, eculizumab is expected to block the activation of the complement system in patients with infection-associated HUS, stopping it from attacking the cells lining the blood vessels. This may reduce damage to the lining of the blood vessel and improve the symptoms of the disease.

What is the stage of development of this medicine?

The effects of eculizumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with eculizumab in patients with infection-associated HUS was ongoing.

At the time of submission, eculizumab was not authorised anywhere in the EU for infection-associated HUS. Orphan designation of the medicine had been granted in the United States of America for Shiga-toxin-producing Escherichia coli HUS.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 May 2012 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.