EU/3/15/1560: Orphan designation for the treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disease that gradually causes weakness and atrophy (wasting) of the muscles. It mainly affects boys, and is usually diagnosed before the age of six years. The muscle weakness usually starts in the hips and legs, before affecting the arms, chest and the heart. Patients with DMD lack normal dystrophin, a protein found in muscles. Because this protein helps to protect muscles from injury as muscles contract and relax, in patients with DMD the muscles become weaker and eventually stop working.

DMD causes long-term disability and is life threatening because of its effects on the heart and the respiratory muscles (muscles that are used to breathe). The disease usually leads to death in adolescence or early adulthood.

At the time of designation, DMD affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of 26,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 512,900,000 (Eurostat 2015).

At the time of designation, Translarna (ataluren) was authorised in the EU to treat patients with DMD who have a specific type of mutation (change) called a nonsense mutation in their dystrophin gene. Patients also received supportive treatment such as physiotherapy.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with DMD; early studies in experimental models indicate that the medicine would not be limited to patients with a specific mutation and would therefore target a wider patient population compared with authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

It is thought that inflammation, particularly inflammation caused by the activity of a protein called 'NF‑κB', leads to muscle damage and prevention of muscle regeneration seen in patients with DMD. This medicine is expected to work by reducing NF-κB activity. This is expected to reduce the muscle damage seen in DMD and enable muscle regeneration.

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 DMD had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for DMD. Orphan designation of the medicine has been granted in the United States for the treatment of DMD.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 3 September 2015 recommending the granting of this designation.

• 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.