EU/3/08/560: Orphan designation for the treatment of moderate and severe closed traumatic brain injury

Closed traumatic brain injury is brain damage caused by a head injury (such as a blow to the head in a traffic accident or a fall). 'Closed' means that the skull remains intact. The initial injury to the head and brain usually goes on to cause 'secondary' problems, most frequently due to bleeding or swelling of the brain tissue (oedema) increasing the pressure within the skull. Traumatic brain injury is classified as minor, moderate or severe according to the patient's symptoms: patients with moderate injury are lethargic (lacking in energy) or stuporous (unaware of their surroundings), and those with severe injury are comatose (unconscious). People with moderate or severe traumatic brain injury need to be admitted to hospital for observation and examination, in case the condition gets worse.

Moderate and severe traumatic brain injury is chronically debilitating and life-threatening.

At the time of designation, moderate and severe closed traumatic brain injury affected less than 4 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 201,000 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 502,800,000 (Eurostat 2008).

Various treatments are available to reduce pressure in within the skull in patients with moderate or severe closed traumatic brain injury, including medicines and surgery.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that (-)-(2R)-3-(2-hydroxymethylindanyl-4-oxy)-phenyl-4,4,4-trifluorobutane-1-sulfonate might be of potential significant benefit for the treatment of moderate and severe closed traumatic brain injury because it has a new mechanism of action. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain orphan status.

This medicine is expected to attach to specific receptors in the brain called 'cannabinoid receptors'. These receptors are involved in the sequence of events that occurs after the initial brain injury that can lead to secondary brain damage. Thus, by activating these “cannabinoid receptors”, this medicine is expected to reduce oedema and to decrease the pressure within the skull.

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

At the time of submission of the application for orphan designation, clinical trials in patients with moderate and severe closed traumatic brain injury were ongoing.
The medicine was not authorised anywhere worldwide for the treatment of moderate or severe closed traumatic brain injury or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 11 June 2008 recommending the granting of the above-mentioned designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.