EU/3/05/278

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Orphan designation

On 27 May 2005, orphan designation (EU/3/05/278) was granted by the European Commission to The Matthews Consultancy Ltd, United Kingdom, for 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid for the treatment of Duchenne muscular dystrophy.

The sponsorship was transferred to Voisin Consulting S.A.R.L., France, in May 2007 and subsequently to PTC Therapeutics Limited, United Kingdom in April 2012.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is Duchenne muscular dystrophy?

Duchenne muscular dystrophy is an inherited genetic disease with onset usually before the age of six. It is characterised by symmetrical progressive diminishing and weakness of the muscles, first at the height of the pelvis and legs. Later on, the muscles of the chest and arms are also involved. Genes located on structures present in each cell of the body (the so-called chromosomes), carry the genetic information that determines the characteristics of each individual. In humans, the so-called X and Y chromosomes determine sex, but carry also other genetic information. Duchenne muscular dystrophy is caused by an abnormality of a gene located on the X chromosome and thus it mainly affects boys. This gene is responsible for the production of a protein, so-called dystrophin, in the muscle cells. This means that patients suffering from this condition do not produce the dystrophin protein or produce non-functional dystrophin. Duchenne muscular dystrophy is chronically debilitating and life-threatening.

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

At the time of designation, Duchenne muscular dystrophy affected approximately 0.36 in 10,000 people in the European Union (EU). This was equivalent to a total of around 17,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

What treatments are available?

At the time of submission of the application for orphan designation, no satisfactory method had been authorised in the EU for treatment of the condition. Treatment of patients with Duchenne muscular dystrophy primarily involves physiotherapy as a supportive treatment.

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?

3-[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid is a medicinal product that might overcome a specific type of abnormality present in the dystrophin gene of some Duchenne patients. Thus, it could enable the production of functional dystrophin protein in the muscle cells of this group of patients.

What is the stage of development of this medicine?

The evaluation of the effects of 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid in experimental models is ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with Duchenne muscular dystrophy had been initiated.

3-[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid was not marketed anywhere worldwide for Duchenne muscular dystrophy at the time of submission. Orphan designation of 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid had been granted in the United States for treatment of muscular dystrophy resulting from premature stop mutations in the dystrophin gene.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 April 2005 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 or not of alternative methods of diagnosis, prevention or treatment;
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still-investigational products that are considered for 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 will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>3-[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid</p>
Active substance3-[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid
Medicine Name
Disease/conditionTreatment of Duchenne muscular dystrophy
Date of decision27/05/2005
OutcomePositive
Orphan decision numberEU/3/05/278

Review of designation

During its meeting of 10 to 12 June 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/05/278 for Translarna (ataluren1) as an orphan medicinal product for the treatment of Duchenne muscular dystrophy. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained2.


1 Previously known as 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-yl]-benzoic acid.
2 The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Translarna for:

‘treatment of Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene, in ambulatory patients aged 5 years and older.’

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of Duchenne muscular dystrophy’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2005. Duchenne muscular dystrophy remains a condition that is long-term debilitating and life threatening, particularly due to heart and respiratory problems. Patients become gradually wheelchair-bound, and the disease usually leads to death in adolescence or early adulthood.

Prevalence of the condition

The sponsor provided updated information on the prevalence of Duchenne muscular dystrophy based on recently published literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of Duchenne muscular dystrophy remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 0.4 people in 10,000. This is equivalent to a total of around 20,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for patients affected by Duchenne muscular dystrophy. Treatment of patients with Duchenne muscular dystrophy primarily involved physiotherapy and other supportive treatments.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Translarna still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Sponsor’s contact details

PTC Therapeutics Limited
16 Great Queen Street
Covent Garden
London
WC2B 5AH
United Kingdom
Tel. +44 (0)20 7486 0111
Fax +44 (0)20 7935 6852

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.