EU/3/01/041: Orphan designation for the treatment of emphysema secondary to 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 emphysema secondary to congenital alpha-1 antitrypsin deficiency affected approximately 2.5 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 94,000 people.

*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. This represents a population of 377,000,000 (Eurostat 2001).

At the time of submission of the application for 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.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that recombinant human alpha-1 antitrypsin might be of potential significant benefit for the treatment of emphysema secondary to congenital alpha-1 antitrypsin deficiency. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary 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 human blood. The product is made into an aerosol, which the patient can inhale. This way, the inhaled protein could reach the lungs where it would replace the natural AAT that is missing and might oppose the effects of elastase. This action is expected to slow down the worsening of the lung disease.

At the time of submission of the application for orphan designation, clinical trials in patients with emphysema secondary to congenital alpha-1 antitrypsin deficiency were ongoing.

AAT was not marketed anywhere worldwide for the treatment of emphysema secondary to congenital alpha-1 antitrypsin deficiency. An orphan designation for this condition was granted in the United States.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 10 April 2001 a positive opinion recommending the grant of the above-mentioned designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.