EU/3/09/613: Orphan designation for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis

Cystic fibrosis is a hereditary (genetic) disease that affects the production of secretions such as mucus in the body. In patients with cystic fibrosis, there is an overproduction of mucus in the lungs, which leads to inflammation and a high risk for the lungs to become infected with bacteria. P. aeruginosa is one of the commonest types of bacteria that infect the lungs of patients with cystic fibrosis.

P. aeruginosa lung infection in cystic fibrosis is a long-term debilitating disease and may be life threatening because it severely damages the lung tissue and does not allow the patient to breathe normally.

At the time of designation, P. aeruginosa lung infection in cystic fibrosis 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 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 511,100,000 (Eurostat 2014).

At the time of submission of the application for orphan drug designation, lung infections in patients with cystic fibrosis were mainly treated with antibiotics (medicines that kill bacteria). These are available as tablets, as infusions (drips into a vein) and solutions for inhalation using a nebuliser (a special machine that changes the solution into an aerosol so that the patient can breathe it in). Other medicines used to treat the lung symptoms of cystic fibrosis included bronchodilators (medicines that help open up the airways in the lungs) and mucolytics (medicines that help to dissolve the mucus). Patients were also advised to exercise and have physiotherapy.

The sponsor has provided sufficient information to show that tobramycin (inhalation use) might be of significant benefit for patients mainly because of the way in which the medicine is given to the patients.This may contribute to the patient care. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Tobramycin is an antibiotic that is already available in the EU as a solution for inhalation for the treatment of P. aeruginosa infection in patients with cystic fibrosis. It works by blocking the bacteria's ribosomes, the parts of the bacterial cells where new proteins are made. By blocking the production of new proteins, the bacteria cannot multiply and they eventually die.

In tobramycin (inhalation use), tobramycin is given to the patient using a new type of nebuliser. The nebuliser is expected to deliver the same amount of antibiotic to the lungs as the existing forms of the medicine, but in a shorter period of time. This is expected to be more convenient for patients, helping them to continue taking their treatment.

The effects of tobramycin (inhalation use) have not been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients had finished, and additional trials were planned.

At the time of submission, tobramycin (inhalation use) was not authorised anywhere in the world for the treatment of P. aeruginosa lung infection in patients with cystic fibrosis or designated as 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 7 January 2009 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 Community) 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 marketing authorisation.