EU/3/05/278: Orphan designation for the treatment of 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.

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).

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.

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.

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.

• 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.