EU/3/18/2048 - orphan designation for treatment of congenital alpha-1 antitrypsin deficiency
N-acetylgalactosamine-conjugated synthetic double-stranded oligomer specific to serpin family A member 1 gene
OrphanHuman
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Overview
On 31 July 2018, orphan designation (EU/3/18/2048) was granted by the European Commission to Pharma Gateway AB, Sweden, for N-acetylgalactosamine-conjugated synthetic double-stranded oligomer specific to serpin family A member 1 gene (also known as ARO-AAT) for the treatment of congenital alpha-1 antitrypsin deficiency.
The sponsorship was transferred to Takeda Pharma A/S in February 2021.
Congenital alpha-1 antitrypsin deficiency is an inherited disease characterised by a lack of normal forms of a protein called ‘alpha-1 proteinase inhibitor’ or ‘alpha-1 antitrypsin’ (AAT).
The liver usually makes AAT. One of the functions of AAT is to protect the lungs from an enzyme called neutrophil elastase. Neutrophil elastase breaks down damaged lung tissue and is produced by white blood cells in response to infection or irritants. In patients lacking AAT, excessive neutrophil elastase activity damages lung tissue and results in emphysema, which causes shortness of breath, coughing and wheezing. Some forms of AAT deficiency can lead to a build-up of defective forms of AAT in liver cells, which can cause severe liver cirrhosis (scarring) often requiring liver transplantation.
Congenital AAT deficiency is a debilitating disease that is long lasting and can be life threatening due to worsening lung function and lung infections as well as liver injury.
At the time of designation, congenital AAT deficiency affected approximately 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 135,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).
At the time of orphan drug designation, the medicine Respreeza, human alpha1-proteinase inhibitor (AAT), given by infusion (drip) into a vein, was authorised in the EU for slowing down the worsening of emphysema caused by congenital AAT deficiency. Patients were also given other medicines to manage the symptoms of obstructive lung disease and help prevent infections of the lungs and the airways.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with congenital AAT deficiency because laboratory studies show that the medicine can treat the liver damage caused by the condition, for which there was no treatment at the time of orphan designation. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine is intended for use in forms of the disease that cause liver damage. It blocks the gene responsible for the production of defective AAT. This is expected to reduce the production of defective AAT and so reduce damage caused by its build-up in the liver.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with congenital AAT deficiency had been started.
At the time of submission, the medicine was not authorised anywhere in the EU for AAT deficiency. Orphan designation of the medicine had been granted in the United States for AAT deficiency.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 June 2018 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.
Key facts
- Active substance
- N-acetylgalactosamine-conjugated synthetic double-stranded oligomer specific to serpin family A member 1 gene
- Intended use
- Treatment of congenital alpha-1 antitrypsin deficiency
- Orphan designation status
- Positive
- EU designation number
- EU/3/18/2048
- Date of designation
- Sponsor
Takeda Pharma A/S
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: