EU/3/15/1605 - orphan designation for treatment of congenital alpha-1 antitrypsin deficiency
Synthetic double-stranded oligomer specific to the SERPINA1 gene and containing a cholesterol-conjugated, acyclic nucleobase analogue
OrphanHuman
Overview
Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in April 2017 on request of the Sponsor.
On 11 January 2016, orphan designation (EU/3/15/1605) was granted by the European Commission to Pharma Gateway AB, Sweden, for synthetic double-stranded oligomer specific to the SERPINA1 gene and containing a cholesterol-conjugated, acyclic nucleobase analogue (also known as ARC-AAT) for the treatment of congenital alpha-1 antitrypsin deficiency.
Congenital alpha-1 antitrypsin deficiency is an inherited disease characterised by a deficiency 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 attack by 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 in the lungs causes destruction of tissue and results in a lung disease called emphysema, which causes symptoms such as shortness of breath, coughing and wheezing. Some forms of the disease can result in accumulation 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 the worsening of lung function and lung infections as well as liver injury.
At the time of designation, congenital AAT deficiency affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 103,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 512,900,000 (Eurostat 2015).
At the time of orphan drug designation, AAT, given by infusion (drip) into a vein, was authorised in the EU for treating 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 of its potential for treating liver injury associated with the disease 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.
Patients with congenital AAT deficiency have a mutation (change) in the SERPINA1 gene, causing deficiency of AAT and in some cases production of a defective protein. This medicine contains a type of synthetic genetic material which prevents the mutated gene from working. This is expected to reduce the production of defective AAT and thereby reduce the damage to liver cells caused by an accumulation of defective AAT.
The synthetic genetic material in the medicine has been attached to cholesterol (a type of fat) which allows the medicine to be taken up easily into the liver cells. In addition, the medicine contains a second substance, melittin-like peptide, which also helps the medicine to be delivered into the liver cells.
The medicine is not likely to be of benefit to patients with lung injury from congenital AAT deficiency.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with congenital AAT deficiency were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for congenital AAT deficiency. Orphan designation of the medicine had been granted in the US for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 December 2015 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
- Synthetic double-stranded oligomer specific to the SERPINA1 gene and containing a cholesterol-conjugated, acyclic nucleobase analogue
- Intended use
- Treatment of congenital alpha-1 antitrypsin deficiency
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/15/1605
- Date of designation
- Sponsor
Pharma Gateway AB
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: