EU/3/05/337

On 23 December 2005, orphan designation (EU/3/05/337) was granted by the European Commission to Vectura Group plc, United Kingdom, for heparin sodium (inhalation use) for the treatment of cystic fibrosis.

What is cystic fibrosis?

Cystic fibrosis is a genetic disease. Genes located on structures (the so-called chromosomes) carry the genetic information that determines the characteristics of each individual. In humans, each cell has 23 pairs of chromosomes. For each pair one chromosome is inherited from the mother, and the other from the father. Cystic fibrosis is caused by abnormalities of a specific gene, called CFTR, carried by the seventh pair of chromosomes. Cystic fibrosis appears only when the CFTR gene is abnormal on both chromosomes of the seventh pair. The CFTR gene is responsible for the production of a protein that regulates the outflow of water and salts (like chloride) from cells that cover internal and external surfaces of the body, the so-called epithelial cells. The defective transport of water and salts, due to the lack of the regulatory protein, results in the thickening of the secretions (mucous) in several organs (e.g. lungs, pancreas). This leads to reduced functioning, chronic infection of the lungs and chronic inflammation (a body response to the injury caused to the tissue). In the long run, these events can induce damage to the lung tissue and the disease can become life threatening.

What are the methods of treatment available?

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 through the mouth, through a vein or they can be inhaled as a fine mist of particles. Other medications to treat the lung disease included bronchodilators, medications that can enlarge the lumen of the airways, and mucolytics, which help to dissolve the lung secretions. Associated treatments included daily exercise and physical therapies and several other types of medications such as pancreatic enzymes and food supplements.
Heparin sodium might be of potential significant benefit for the treatment of cystic fibrosis because it might improve the long-term outcome of patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

What is the estimated number of patients affected by the condition*?

According to the information provided by the sponsor, cystic fibrosis was considered to affect about 60,000 persons in the European Union.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Heparin sodium is a product mainly known by its ability to dissolve blood clots. In addition, the sponsor provided data indicating potential other activities that could be of interest for the treatment of cystic fibrosis patients, such as the ability to break down mucus (mucolytic) and to increase the diameter of the respiratory ways (bronchodilator). The sponsor has developed a formulation for dry powder inhalation to be administered with a commercial device. It is expected that using heparin sodium locally in the airways and having these multiple levels of interactions it might help to reduce the severity of the disease in the long-term.

What is the stage of development of this medicinal product?

The effects of heparin sodium (inhalation use) were evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials in patients with cystic fibrosis were initiated.
Heparin sodium (inhalation use) was not authorised anywhere worldwide for treatment of cystic fibrosis or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 10 November 2005 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• the seriousness of the condition,
• the existence or not of alternative methods of diagnosis, prevention or treatment and 
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for 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 will be necessary before this product can be granted a marketing authorisation.