EU/3/12/1045: Orphan designation for the treatment of cystic fibrosis

Cystic fibrosis is a hereditary disease that affects the cells in the lungs and the glands in the gut and pancreas that secrete fluids such as mucus and digestive juices. In cystic fibrosis, these fluids become thick and viscous, blocking the airways and the flow of digestive juices. 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 recurrent chest infections.

At the time of designation, cystic fibrosis affected approximately 0.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 35,000 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).

At the time of designation, lung infection in cystic fibrosis was mainly treated with antibiotics. Other medicines used to treat the lung disease included anti-inflammatory agents, 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 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 this medicine might be of significant benefit for patients with cystic fibrosis because it works in a different way to existing treatments and early studies in patients with cystic fibrosis suggest that may improve the outcome 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.

Patients with cystic fibrosis have excessive amounts of the enzyme elastase in their lungs. Elastase is usually produced as part of the inflammatory response and is inactivated by a protein called alpha-1 proteinase inhibitor (also known as alpha-1 antitrypsin). In cystic fibrosis, not all elastases are inactivated as they should, and therefore remain active causing inflammation and lung damage.

This medicine is made of alpha-1 proteinase inhibitor derived from the blood of human donors. By giving additional alpha-1 proteinase inhibitor (via inhalation), it is expected that additional elastases can be inactivated, thereby reducing the amount of active elastases and in turn the damage to the lungs in patients with cystic fibrosis.

The effects of alpha-1 proteinase inhibitor have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with alpha-1 proteinase inhibitor in patients with cystic fibrosis were ongoing.

At the time of submission, alpha-1 proteinase inhibitor was not authorised anywhere in the EU for cystic fibrosis. Orphan designation had been granted in the United States of America for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 September 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.