EU/3/08/546: Orphan designation for the treatment of congenital alpha-1 antitrypsin deficiency

Congenital alpha-1 antitrypsin deficiency is an inherited disease that is characterised by a lack (deficiency) of a protein in the blood called 'alpha-1 proteinase inhibitor' or 'alpha-1 antitrypsin' (AAT). AAT is produced in the liver and its main function is to control another protein called elastase. Elastase is an enzyme that breaks down a cell constituent, elastin, which is present in the lungs. Because AAT is missing in patients with congenital alpha-1 antitrypsin deficiency, elastase can accumulate in the lungs, and the patients can develop a lung disease called emphysema, resulting in shortness of breath, coughing and wheezing.

Congenital AAT deficiency is a debilitating disease that is long lasting and can be life-threatening.

At the time of designation, congenital AAT deficiency affected approximately 2.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 126,000 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 (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 502,800,000 (Eurostat 2008).

At the time of orphan drug designation, treatment for lung disease due to AAT deficiency included medicines that help patients to breathe, oxygen, and medicines containing human AAT given as an injection into a vein. In the most severe cases of lung disease, a lung transplant might be considered.

The sponsor has submitted satisfactory argumentation to justify the assumption that alpha-1 proteinase inhibitor (for inhalation use) might be of benefit for the treatment of congenital AAT deficiency because it can be administered by breathing. This assumption will need to be confirmed at the time of marketing authorisation, to maintain the orphan status of the medicine.

Alpha-1 proteinase inhibitor (for inhalation use) contains human AAT in a form that can be breathed directly into the lungs. In the lungs, it works in the same way as AAT to replace the missing enzyme and stopping the accumulation of elastase. This helps to reduce the symptoms of lung disease due to AAT deficiency.

The effects of alpha-1 proteinase inhibitor (for inhalation use) have been evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials in patients with congenital AAT deficiency were ongoing.

At the time of submission, alpha-1 proteinase inhibitor (for inhalation use) was not authorised anywhere in the world for congenital AAT deficiency or designated as orphan medicinal product elsewhere for this condition.

According to Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 April 2008 recommending the granting of the above-mentioned designation.

• the seriousness of the condition;
• the existence or not of alternative methods of diagnosis, prevention or treatment;
• 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.