EU/3/08/566: Orphan designation for the treatment of cystic fibrosis

Cystic fibrosis is a hereditary (genetic) disease that affects the production of secretions (such as mucus) from the glands in the body. It affects the lungs and the digestive system (gut) in particular. Cystic fibrosis is caused by abnormalities in a gene called 'cystic-fibrosis transmembrane-conductance regulator' (CFTR). The CFTR gene is responsible for the production of CFTR, a protein that regulates the production of mucus and digestive juices by acting as a chloride ion channel to allow proper movement of salt and water in and out of certain cells in the lungs and other tissues. In patients with cystic fibrosis, there is an overproduction of mucus in the lungs and a reduced production of digestive juices from the pancreas (an organ near the stomach). This leads to long-term infection and inflammation of the lungs and problems with the digestion and absorption of food resulting in poor growth.

Cystic fibrosis is a long-lasting and life-threatening disease.

At the time of designation, cystic fibrosis affected approximately 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 65,000 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).

At the time of submission of the application for orphan-drug designation, lung infection and inflammation in cystic fibrosis were mainly treated with physiotherapy and antibiotics. Other medicines used to treat the lung disease included bronchodilators (medicines that help to open up the airways in the lungs) and mucolytics (medicines that help dissolve the mucus in the lungs). In addition, patients were often given other types of medicine, such as pancreatic enzymes (substances that help to digest and absorb food) and food supplements. They are also advised to exercise and to undergo physiotherapy.

The sponsor has provided sufficient information to show that levofloxacin hemihydrate might be of significant benefit for the patients because it could improve the treatment of lung infection in cystic fibrosis and could be inhaled quickly. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Levofloxacin hemihydrate is an antibiotic that belongs to the group 'fluoroquinolones'. It works by blocking an enzyme that bacteria use to make more DNA. By doing this, it stops the bacteria that are causing an infection from growing and multiplying. Levofloxacin hemihydrate is currently used to treat various infections as an intravenous infusion or tablets. This sponsor is developing a product containing levofloxacin hemihydrate for inhalation for the treatment of lung infections in patients with cystic fibrosis.

The effects of levofloxacin hemihydrate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with cystic fibrosis were ongoing.

The medicinal product was not authorised anywhere in the world for cystic fibrosis at the time of submission. Orphan designation of this product had been granted in the United States for the treatment of lung infections due to Pseudomonas aeruginosa and other bacteria in patients with cystic fibrosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 July 2008 recommending the granting of this 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.