EU/3/15/1498 - orphan designation for treatment of cystic fibrosis

2-(7-ethoxy-4-(3-fluorophenyl)-1-oxophthalazin-2(1H)-yl)-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl) acetamide

Overview

Please note that this product was withdrawn from the Union Register of orphan medicinal products in April 2020 on request of the sponsor.

On 21 May 2015, orphan designation (EU/3/15/1498) was granted by the European Commission to Clinical Network Services (UK) Ltd, United Kingdom, for 2-(7-ethoxy-4-(3-fluorophenyl)-1-oxophthalazin-2(1H)-yl)-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl)acetamide for the treatment of cystic fibrosis.

The sponsorship was transferred to Clinical Network Services (NL) B.V., The Netherlands, in January 2019.

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 defects ('mutations') 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 the condition?

At the time of designation, cystic fibrosis affected approximately 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 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 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, lung infection in cystic fibrosis was mainly treated with antibiotics. Kalydeco (ivacaftor) was authorised to treat a subgroup of patients with cystic fibrosis who have certain mutations in the gene for the CFTR protein. 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 this medicine might be of significant benefit for patients with cystic fibrosis because early studies in experimental models suggest that the medicine may correct the function of the defective CFTR protein in patients with the most common form of mutation (F508d). 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?

Patients with cystic fibrosis due to the most common CFTR mutation, F508d, produce badly shaped CFTR protein which does not work properly and is quickly broken down and destroyed. The medicine is expected to help correct the way in which the protein is shaped and allow it to work better and be more stable. This should reduce the thickness of mucus and digestive juices, thereby improving the symptoms of the disease.

What is the stage of development of this medicine?

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 cystic fibrosis had been started.

At the time of submission, the medicine 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 16 April 2015 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/3/15/1498: Public summary of opinion on orphan designation: 2-(7-ethoxy-4-(3-fluorophenyl)-1-oxophthalazin-2(1H)-yl)-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl) acetamide for treatment of cystic fibrosis

Adopted Reference Number: EMA/COMP/274375/2015

Key facts

• Active substance:
  2-(7-ethoxy-4-(3-fluorophenyl)-1-oxophthalazin-2(1H)-yl)-N-methyl-N-(2-methylbenzo[d]oxazol-6-yl) acetamide
• Intended use:
  Treatment of cystic fibrosis
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/15/1498
• Date of designation:
  21/05/2015
• Sponsor:

  Scendea (NL) B.V.

Review of designation

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