EU/3/03/140: Orphan designation for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis

Cystic fibrosis is a genetic 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 CFTR, carried by the 7th pair of chromosomes. 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. Cystic fibrosis appears only when the CFTR is abnormal on both chromosomes of the 7th pair. The defective transport of water and salts due to the lack of the regulatory protein results in the thickening of the secretions in several organs (e.g. lungs, pancreas). This leads to chronic infection of the lungs and chronic inflammation (a response to the injury caused to the tissue). Pseudomonas aeruginosa is a species of bacteria (micro-organisms that can cause certain types of infections). Chronic infection of the lung with Pseudomonas aeruginosa is a typical feature of cystic fibrosis. It can induce damage to the lung tissue and respiratory insufficiency, which is life threatening.

At the time of designation, Pseudomonas aeruginosa lung infection in cystic fibrosis affected approximately 1.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50,000 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).

*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. At the time of designation, this represented a population of 382,800,000 (Eurostat 2003).

Pseudomonas aeruginosa lung infection in cystic fibrosis is treated mostly with antibiotic (drugs that kill micro-organisms) therapy administered by a variety of routes, oral, intravenous and as an aerosol via nebulisation. Several antibiotics had been authorised for the condition in some countries in the Community, at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that tobramycin (inhalation powder) might be of potential significant benefit for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis, particularly in regards to a contribution to patient care. The assumption of benefit is yet to be validated and will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Tobramycin is an antibiotic produced by certain strains of bacteria with activity against a wide range microorganisms including Pseudomonas aeruginosa. The sponsor has developed a formulation for dry powder inhalation to be administered with a commercial device. It acts by disrupting protein synthesis and this kills the microorganisms.

The evaluation of the effects of tobramycin (inhalation powder) in experimental models is ongoing.

At the time of the submission of the application for orphan designation clinical trials with tobramycin inhalation powder in cystic fibrosis patients with Pseudomonas aeruginosa lung infection had not been initiated.

Tobramycin inhalation powder was not marketed anywhere worldwide for the condition, at the time of submission and has not been submitted or approved for a marketing authorisation in any country.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 February 2003 recommending the granting of this designation.

Update: tobramycin (inhalation powder) (Tobi Podhaler) has been authorised in the EU since 20 July 2011 for the suppressive therapy of chronic pulmonary infection due to Pseudomonas aeruginosa in adults and children aged 6 years and older with cystic fibrosis.

• 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.