EU/3/07/469: Orphan designation for the treatment of cystic fibrosis

Cystic fibrosis is a genetic disease caused by abnormalities of a specific gene, called CFTR. Cystic fibrosis appears only when both copies of the CFTR gene are abnormal (a situation called homozygosis). The CFTR gene is responsible for the production of a protein that regulates the passage of water and salts (like chloride) from and to specific cells of the body (epithelial cells). If the CFTR gene is abnormal there is defective transport of water and salts, which in turn results in the thickening of the secretions in several organs, particularly in the lungs and in the pancreas. This leads to accumulation of phlegm (mucus) in the lung and to chronic infections and chronic inflammation of the lung tissues. In the long term, these events and acute reactivations of the lung infections can induce damage to the lung tissue; the disease is life threatening due to the reduced lung function.

At the time of designation, cystic fibrosis affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 46,000 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 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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

At the time of submission of the application for the orphan drug designation, lung infection and inflammation in cystic fibrosis were treated mainly with antibiotics. These can be taken in a number of ways such as by mouth, intravenous infusion or they can be inhaled as a fine mist of particles. Other medications to treat the lung disease included bronchodilators (medications that enlarge the width of the airways) and mucolytics (that help to dissolve the lung secretions). Associated treatments included daily exercise and physiotherapy and several other types of medications such as pancreatic enzymes and food supplements.

Ciprofloxacin (inhalation use) might be of potential significant benefit for the treatment of cystic fibrosis because it might improve the long-term outcome of patients by reducing acute exacerbations of the lung infection. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Ciprofloxacin is an antibiotic, which is authorised for the short-term systemic treatment of acute exacerbations of infections in cystic fibrosis. The inhalation form is expected to target the lung directly, allowing a reduction of the dose to be administered compared to oral treatment. Targeted inhalation treatment may also reduce the occurrence of bacterial resistance due to long-term treatment with antibiotics from different classes.

The evaluation of the effects of ciprofloxacin (inhalation use) in experimental models is ongoing. At the time of submission of the application for orphan designation, no clinical trials in patients with cystic fibrosis were initiated.

Ciprofloxacin (inhalation use) was not authorised anywhere in the world for cystic fibrosis or designated as orphan elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 27 June 2007 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 a marketing authorisation.