EU/3/20/2282: 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, Duchenne muscular dystrophy affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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).

At the time of designation, the medicine Translarna (ataluren) was authorised in the EU for the treatment of a 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 studies indicate that the medicine may improve muscle function in patients with several other mutations in the dystrophin gene. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Several mutations in the dystrophin gene prematurely stop the production of a normal dystrophin protein, leading to a shortened protein that does not function properly. This medicine is an antisense oligonucleotide (a small strand of synthetic genetic material). It is expected to work in patients with a deletion mutation (where a piece of the gene is missing) by enabling the protein-making apparatus in cells to move past the mutation, allowing the cells to produce a functional protein.

The effects of viltolarsen have been evaluated in experimental models.

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

At the time of submission, viltolarsen was not authorised anywhere in the EU for the treatment of DMD or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 23 April 2020, 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.