EU/3/15/1607: Orphan designation for the treatment of acute radiation syndrome

Acute radiation syndrome (also known as radiation sickness) is a severe illness caused by exposure of the body to a high dose of radiation in a very short period of time. This can occur, for example, following an accident at a nuclear power plant or the use of radioactive material for medical purposes.

Symptoms can begin within a few hours after exposure and their severity depends on the amount of radiation absorbed by the body. Relatively small amounts result in gastrointestinal effects such as nausea (feeling sick), vomiting and diarrhoea, reduction in blood cell count, and tendency to infection and bleeding. Relatively large amounts can result in effects on the central nervous system (brain and spinal cord) and rapid death.

Acute radiation syndrome is a life-threatening condition because it can lead to failure of multiple organs and death.

At the time of designation, acute radiation syndrome affected less than 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 500 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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of acute radiation syndrome.

Entolimod is expected to work by attaching to a protein on the surface of body cells known as toll-like receptor 5 (TLR5). The attachment to TLR5 triggers the release of substances, whose effects include regeneration of tissue and increased cell survival. These effects are expected to reduce the damage caused by radiation to cells in the bone marrow and gastrointestinal tract, lowering the risk of bleeding and infection and thereby helping to improve recovery.

The effects of entolimod have been evaluated in experimental models. For ethical reasons, no clinical trials in patients with acute radiation syndrome are planned.

At the time of submission of the application for orphan designation, the medicine was not authorised anywhere in the EU for acute radiation syndrome. Orphan designation had been granted in the United States for preventing death following a potentially lethal dose of radiation in a radiation disaster.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 December 2015 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.