EU/3/10/782: Orphan designation for the treatment of cystic fibrosis

Cystic fibrosis is a hereditary disease that affects the production of secretions such as mucus in the body. In patients with cystic fibrosis, there is an over-production of mucus in the lungs and a reduced production of digestive juices from the pancreas (an organ near the stomach). This leads to problems with the digestion and absorption of food, resulting in poor growth, and long-term infection and inflammation of the lungs because of excess mucus not being cleared away.

Cystic fibrosis is a long-lasting and life-threatening disease because it severely damages the lung tissue, which leads to problems with breathing and results in shortened life expectancy.

At the time of designation, cystic fibrosis affected approximately 1.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 66,000 people, and is below the threshold 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. This represents a population of 506,500,000 (Eurostat 2010).

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

The sponsor has provided sufficient information to show that nafamostat mesilate might be of significant benefit for patients with cystic fibrosis because it works in a different way to existing treatments and because early studies indicate that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In the airways of patients with cystic fibrosis, the activity of a protein called the epithelial sodium channel (ENaC) is increased. This contributes to the inability of these patients to clear excessive mucus from their airways. Nafamostat mesilate is expected to work by reducing ENaC activity, stimulating the clearance of mucus and relieving the symptoms of the disease. The medicine is expected to be given as an inhaled aerosol.

At the time of submission of the application for orphan designation, the evaluation of the effects of nafamostat mesilate in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials with nafamostat mesilate in patients with cystic fibrosis had been started.

At the time of submission, nafamostat mesilate was not authorised anywhere in the EU for cystic fibrosis 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 2 June 2010 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.