EU/3/13/1195 - orphan designation for treatment of cystic fibrosis

antisense oligonucleotide targeting the F508delta mutation of CFTR (eluforsen)

Overview

This medicine is now known as eluforsen.

On 7 October 2013, orphan designation (EU/3/13/1195) was granted by the European Commission to ProQR Therapeutics BV, The Netherlands, for antisense oligonucleotide targeting the F508delta mutation of CFTR for the treatment of cystic fibrosis.

The sponsorship was transferred to ProQR Therapeutics III BV, The Netherlands, in January 2016.

Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2020 on request of the Sponsor.

What is cystic fibrosis?

Cystic fibrosis is a hereditary disease that affects the cells in the lungs, and the glands in the gut and pancreas, that secrete fluids such as mucus and digestive juices. In cystic fibrosis, these fluids become thick and viscous, blocking the airways and the flow of digestive juices. This leads to long-term infection and inflammation of the lungs because of excess mucus not being cleared away, and to problems with the digestion and absorption of food, resulting in poor growth.

Cystic fibrosis is caused by abnormalities in a gene that makes a protein called 'cystic-fibrosis transmembrane conductance regulator' (CFTR), which is involved in regulating the production of mucus and digestive juices.

Cystic fibrosis is a long-term debilitating and life-threatening disease because it severely damages the lung tissue, leading to problems with breathing and to recurrent chest infections.

What is the estimated number of patients affected by this condition?

At the time of designation, cystic fibrosis affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 36,000 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).

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*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 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, lung infection in cystic fibrosis was mainly treated with antibiotics. Kalydeco (ivacaftor) was authorised to correct the defect of the CFTR protein in a subgroup of patients with cystic fibrosis with the G551D mutation. Other medicines used to treat the lung disease included anti-inflammatory agents, bronchodilators (medicines that help to open up the airways in the lungs) and mucolytics (medicines that help dissolve the mucus in the lungs). In addition, patients with cystic fibrosis were often given other types of medicines such as pancreatic enzymes (substances that help to digest and absorb food) and food supplements. They were also advised to exercise and to undergo physiotherapy.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients based on data from laboratory studies suggesting that it may lead to the production of a normal CFTR protein in patients with the F508delta mutation in their CFTR genes. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is an 'anti-sense oligonucleotide', a very short piece of synthesized RNA (a type of genetic material involved in the production of proteins). This anti-sense RNA specifically attaches to the 'sense' RNA with the F508delta mutation which is responsible for the production of the abnormal CFTR protein in cystic fibrosis. As a result, the anti-sense RNA is expected to induce the repair of the genetic RNA abnormality, leading to the production of a fully functional CFTR protein. When given by inhalation, the medicine is expected to slow down or stop further damage to the lungs and relieve the symptoms of cystic fibrosis.

What is the stage of development of this medicine?

The effects of the medicinal product have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicinal product in patients with cystic fibrosis had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for cystic fibrosis or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 September 2013 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria

• 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.

EU/3/13/1195: Public summary of opinion on orphan designation:Antisense oligonucleotide targeting the F508delta mutation of CFTR for the treatment of cystic fibrosis

Adopted Reference Number: EMA/COMP/562059/2013

Key facts

• Active substance:
  antisense oligonucleotide targeting the F508delta mutation of CFTR (eluforsen)
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/13/1195
• Date of designation:
  07/10/2013
• Sponsor:

  ProQR Therapeutics III BV; Zernikedreef 9; 2333 CK Leiden; The Netherlands; Tel. [phone]; E-maiil: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.