EU/3/01/044: 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, congenital alpha-1-antitrypsin deficiency affected approximately 2.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 94,000 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).

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.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that human alpha-1-proteinase inhibitor 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.

Human alpha-1-proteinase inhibitor is derived from blood. The resulting human alpha-1-proteinase inhibitor is made into an aerosol, which the patient can inhale. In this way, the inhaled protein could reach the lungs, where it would restore the missing levels of AAT. Thus, the inhaled human alpha-1-proteinase inhibitor could oppose the effects of elastase. This action is expected to slow down the worsening of the lung disease.

The effects of human alpha-1-proteinase inhibitor were evaluated in experimental models.

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.

The designated medicinal product was not marketed anywhere worldwide for treatment of emphysema secondary to congenital alpha-1-antitrypsin deficiency, at the time of submission. Orphan designation of human alpha1-proteinase inhibitor (respiratory use) was granted in the United States for emphysema in alpha-1-antitrypsin deficient patients.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 May 2001 recommending the granting of this 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.