EU/3/05/278

On 27 May 2005, orphan designation (EU/3/05/278) was granted by the European Commission to The Matthews consultancy Ltd, UK, 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.

The sponsorship was transferred to PTC Therapeutics Limited, United Kingdom in April 2012.

What is Duchenne muscular dystrophy?

Duchenne muscular dystrophy is an inherited genetic disease with onset usually before the age of 6. It is characterised by symmetrical progressive diminishing and weakness of the muscles, first at the height of the pelvis and legs, later on also the muscles of the chest and arms are 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 the 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 affects mainly boys. This gene is responsible for the production of a protein, the so-called dystrophin, in the muscle cells. This means that patients suffering from this condition do not produce the dystrophin protein or produce a 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 is equivalent to a total of around 18,227 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

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

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 which 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 were 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 was granted in the United States for treatment of muscular dystrophy resulting from premature stop mutations in the dystrohin 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 and 
• 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 which were 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.