EU/3/04/230 - orphan designation for treatment of cystic fibrosis

Dexamethasone sodium phosphate encapsulated in human erythrocytes

Overview

On 20 October 2004, orphan designation (EU/3/04/230) was granted by the European Commission to Dideco S.p.A., Italy for dexamethasone sodium phosphate encapsulated in human erythrocytes for the treatment of cystic fibrosis.

The sponsor changed name to Sorin Group Italia S.r.l., Italy, in December 2005 and subsequently to Erydel S.p.A., Italy, in January 2010.

What is cystic fibrosis?

Cystic fibrosis is an inherited disease. The genetic information that determines the characteristics of each individual is carried by genes located on structures called chromosomes. 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 cystic CFTR, carried by the seventh pair of chromosomes. Cystic fibrosis appears only when the CFTR is abnormal on both chromosomes of the seventh pair. The CFTR gene is responsible for the production of a protein that regulates 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 and 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 is the estimated number of patients affected by the condition?

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 60,000 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).

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*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).

What treatments are 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. Associated treatments included daily exercise and physical therapies and several other types of medications such as pancreatic enzymes and food supplements. Bronchodilators are medications that can enlarge the lumen of the airways. Mucolytics help to dissolve the secretions. Still other medications were used to fight the inflammation. Dexamethasone sodium phosphate encapsulated in human erythrocytes might be of potential significant benefit for the treatment of cystic fibrosis because it can act in a different way than other available treatments. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Dexamethasone sodium phosphate encapsulated in human erythrocytes belongs to a group of substances called corticosteroids that have an anti-inflammation activity. Dexamethasone sodium phosphate is supposed to act by reducing the chronic inflammation present at the level of the lungs. This product acts by reducing the release of substances involved in inflammation called cytokines from the white blood cells. The dexamethasone salt is wrapped (encapsulated) in red blood cells (human erythrocytes) as they have the function of delivering low quantities of dexamethasone over a longer period of time.

What is the stage of development of this medicine?

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

Dexamethasone sodium phosphate for encapsulated in human erythrocytes was not marketed anywhere worldwide for 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 9 September 2004 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/04/230: Public summary of positive opinion for orphan designation of dexamethasone sodium phosphate encapsulated in human erythrocytes for the treatment of cystic fibrosis

AdoptedReference Number: EMEA/COMP/77487/2004

Key facts

• Active substance:
  Dexamethasone sodium phosphate encapsulated in human erythrocytes
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/04/230
• Date of designation:
  20/10/2004
• Sponsor:

  Erydel S.p.A.; Via Sasso, 36; 61029 Urbino; Italy; Tel. [phone]; Fax [phone]; E-mail: [e-mail]