EU/3/18/2021: Orphan designation for the prevention of 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. HUS can lead to formation of blood clots that damage small vessels supplying the organs and may cause problems in the brain and nervous system, and damage to other organs such as the heart and gut.

HUS is often associated with bacterial infections that produce a toxin called Shiga toxin and over-activate the complement system, part of the immune system. This damages the lining of the blood vessels, triggering the symptoms of the disease. Infection-associated HUS usually occurs in children, and is most often caught through an infected food source.

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

At the time of designation, the number of patients at risk of HUS was estimated to be approximately 0.2 people in 10,000 in the European Union (EU). This was equivalent to a total of around 10,000 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 at risk of developing 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 517,400,000 (Eurostat 2018).

At the time of designation no satisfactory methods of prevention for HUS were authorised in the EU. The medicine Soliris was authorised to treat patients who developed certain (atypical) forms of the condition, while patients who developed infection-related HUS were managed with supportive treatment. Transfusions of red blood cells and platelets were given as needed, as well as medicines to manage complications such as seizures (fits). Dialysis (a blood clearance technique) was used if the disease progressed to kidney failure. Some patients needed a kidney transplant.

The medicine contains fragments of an antibody (a type of protein) obtained from horses that have been immunised against Shiga toxin. Shiga toxin is a substance produced by bacteria that cause infection-related HUS and is thought to be linked to the development of the condition. When the fragments of antibody are given to a patient thought to be at risk of developing HUS, they attach to any Shiga toxin present and stop it from acting. This is expected to prevent the overactivity of the complement system and damage to blood vessels that leads to HUS.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with HUS had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for HUS or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 April 2018 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.