EU/3/08/586: Orphan designation for the treatment of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an inherited genetic disease characterised by progressive weakening of the muscles. It mainly affects boys, usually before the age of six years. The muscle weakness starts in the hips and legs, before reaching the chest, arms, and possible heart, later on. Patients with DMD do not produce enough of a protein called dystrophin. As dystrophin is an important component of muscle fibres, the muscles of patients with DMD cannot grow, so they become weak and eventually stop working.

DMD causes long-term disability and is life-threatening because of its effects on the heart and on respiratory muscles (muscles that are used to breathe).

At the time of designation, DMD affected approximately 0.3 in 10,000 people in the European Union (EU)*. This is below the threshold for orphan designation which is 5 in 10,000, and is equivalent to a total of around 15,000 people. This is based on the information provided by the sponsor and 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 based on data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 502,282,000 (Eurostat 2008).

At the time of submission of the application for orphan drug designation, there were no treatments available in the EU that could cure DMD. The main treatments for the disease were corticosteroids to slow down the progression of the disease, and physiotherapy, which was used to relieve symptoms and improve the patient's general condition.

The sponsor has provided sufficient information to show that RNA, [P-deoxy-P-(dimethylamino)] (2',3'-dideoxy-2',3'-imino-2',3'-seco) (2'a→5')(C-m5U-C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G),P-[4-[[2-[2-(2hydroxyethoxy)ethoxy]ethoxy]carbonyl]-1-piperazinyl]-N,N-dimethylaminophosphonamidate might be of potential significant benefit for patients because of the way the medicine is expected to work. This could improve the overall outcome of patients with DMD. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is thought to promote the production of a truncated (shortened) form of the dystrophin protein. This truncated protein is expected to act in a similar way to the full dystrophin protein, helping the body to make up for the loss of dystrophin, and relieving the symptoms of DMD.

The effects of RNA, [P-deoxy-P-(dimethylamino)] (2',3'-dideoxy-2',3'-imino-2',3'-seco) (2'a→5')(C-m5U-C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G),P-[4-[[2-[2-(2hydroxyethoxy)ethoxy]ethoxy]carbonyl]-1-piperazinyl] N,N-dimethylaminophosphonamidate have been evaluated in experimental models.

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

Orphan designation of this product had been granted in the United States for DMD.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 October 2008 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 Community) 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 marketing authorisation.