EU/3/17/1965: 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 muscles. It mainly affects boys, and usually starts 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 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 around 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 515,700,000 (Eurostat 2017).

At the time of designation, the medicine Translarna (ataluren) was authorised in the EU for the treatment of a small group of patients with DMD caused by a particular type of mutation (change), called a nonsense mutation, in the 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 because early data indicate that it could slow down the decline in muscle function in a wider patient population than with the authorised treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains metformin and L-citrulline. In DMD, metformin is thought to protect muscle function by increasing the action of AMP-activated protein kinase (AMPK), an enzyme that regulates the energy balance of cells, including muscle cells. L-citrulline has been shown to reduce muscle wasting. The combined actions of metformin and L-citrulline are expected to help improve muscle function and slow down the progression of the disease.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with DMD were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for DMD 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 7 December 2017 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.