EU/3/14/1304:

Myasthenia gravis is a disease that leads to muscle weakness and tiredness. It is an immune disorder in which the immune system (the body's natural defences) attacks and damages 'acetylcholine receptors' on the surface of muscle cells. For a muscle to contract, a substance called acetylcholine is released from a nerve and attaches to the acetylcholine receptors on the muscle cells. In myasthenia gravis, because of the damage to these receptors, the muscles are not able to contract as well as normal. In most patients, the disease is associated with abnormalities of a gland in the chest called the thymus, which is part of the immune system.

In myasthenia gravis, the muscles involved in swallowing and those around the eyes are commonly affected first, causing difficulty in swallowing and the eyelids to droop. Muscle weakness typically worsens towards the end of the day and after exercise.

Myasthenia gravis is a long-term debilitating disease and may be life-threatening when the muscles involved in breathing are affected.

At the time of designation, myasthenia gravis affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 103,000 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. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).

At the time of designation, a number of medicines were authorised in the EU for the treatment of myasthenia gravis. Surgery to remove the thymus gland (thymectomy) was performed in some patients.

The sponsor has provided sufficient information to show that eculizumab might be of significant benefit for patients with myasthenia gravis because it works in a different way to existing treatment and early studies indicate that it might benefit patients in whom other treatments have stopped working. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status

Eculizumab is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) that is found in the body. It works by attaching to and blocking the action of a protein called 'C5 complement protein', which is involved in the immune reactions that can cause damage to acetylcholine receptors on the muscle cells. By reducing damage to acetylcholine receptors, the medicine is expected to improve muscle contraction, thereby reducing symptoms of the disease.

The effects of eculizumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with eculizumab in patients with myasthenia gravis was ongoing.

At the time of submission, eculizumab was not authorised anywhere in the EU for myasthenia gravis 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 12 June 2014 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.