EU/3/14/1383

On 16 December 2014, orphan designation (EU/3/14/1383) was granted by the European Commission to Coté Orphan Consulting UK Limited, United Kingdom, for single-chain urokinase plasminogen activator for the treatment of pleural empyema.

What is pleural empyema?

Pleural empyema is a condition in which a bacterial lung infection spreads to the space between the pleura, the two layers of membrane that surround the lung inside the chest. This space becomes filled with fluid and dead cells as well as deposits of a protein called fibrin, producing pockets of thick pus. The pus and fibrin build-up make it harder to breathe properly and eventually lead to the formation of scar tissue that permanently reduces normal lung function.

Pleural empyema is a long-term debilitating and life-threatening condition due to restriction of the normal expansion of the lung.

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

At the time of designation, pleural empyema affected approximately 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 66,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of designation, various antibiotics were authorised in the EU for the treatment of lung infections, which would include infections that spread to the pleura. In addition, patients were offered chest drainage, to remove the fluid and pus, or other surgery as appropriate.

The sponsor has provided sufficient information to show that single-chain urokinase plasminogen activator might be of significant benefit for patients with pleural empyema because experimental data show that it works in a different and complementary way to existing treatments by reducing the formation of fibrin that makes the pleura stick together. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

In patients with pleural empyema, inflammation due to the infection triggers deposits of fibrin in the fluid between the two pleura, sticking them together (adhesion) so they cannot move so easily. This creates pockets where pus can collect that are difficult to drain and into which antibiotics cannot penetrate easily. The medicine converts another protein in the body, plasminogen, into its active form plasmin which is able to break down and dissolve fibrin. Giving the medicine directly into the space between the pleura is therefore expected to result in breakdown of the fibrin there, enabling the pus to be drained and antibiotics to penetrate the space, so improving the symptoms of the condition.

What is the stage of development of this medicine?

The effects of single-chain urokinase plasminogen activator 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 pleural empyema had been started.

At the time of submission, single-chain urokinase plasminogen activator was not authorised anywhere in the EU for pleural empyema 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 13 November 2014 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.