EU/3/02/100: Orphan designation for the treatment of emphysema secondary to congenital alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin (AAT) is a protein that normally inhibits the activity of certain enzymes in the blood. One of these enzymes is elastase. The action of elastase is to destroy certain molecules that form the lung tissue. AAT controls this action of elastase. If AAT is missing then the action of elastase is no longer opposed. In the long term, this may damage the lungs and cause lung disease. Severe deficiency of AAT is related to parent's genetic input. Lung disease due to this deficiency is also called 'hereditary emphysema'. The condition is chronically debilitating and life-threatening.

At the time of designation, emphysema secondary to congenital alpha-1 antitrypsin deficiency affected approximately 2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 101,260 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 380,600,000 (Eurostat 2002).

Therapy for lung disease due to AAT deficiency includes the use of drugs to help breathing, hormones and drugs to help clear mucus. Lung infections will require prompt treatment with antibiotics. Human AAT to be administered intravenously has also been available in some countries in Europe. The drug has been obtained from human blood and needs to be injected into a vein. Oxygen may also be given in the more advanced stages and lung transplantation is used as a last resource.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Recombinant human AAT is a protein that is produced in yeast using combinations of genes. The resulting AAT is similar to the natural protein found in the blood. The product is made into an aerosol, which the patient can inhale. In this way, the inhaled protein could reach the lungs where it would replace the natural AAT that is missing. In this way the inhaled AAT could oppose the effects of elastase. This action is expected to slow down the worsening of the lung disease.

The evaluation of the effects of recombinant human AAT in experimental models is ongoing. Studies in patients have not started yet.

At the time this orphan designation was submitted, the product had not been marketed anywhere in the world.

An orphan designation for this condition has been granted in the United States.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 26 March 2002 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.