EU/3/09/689

On 9 November 2009, orphan designation (EU/3/09/689) was granted by the European Commission to CuraVac Europe SPRL, Belgium, for peptides mimicking antigen receptors on autoimmune B cells and autoimmune T cells associated with myasthenia gravis for the treatment of myasthenia gravis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 September 2009 recommending the granting of this designation.

What is myasthenia gravis?

Myasthenia gravis is a disease that leads to muscle weakness and tiredness. It is caused by the immune system (the body’s natural defences) producing abnormal antibodies (types of proteins) that damage proteins called ‘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 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.
In most patients, the abnormal antibody production is associated with abnormalities of a gland in the chest called the thymus, which is part of the immune system.
Myasthenia gravis is a long-term debilitating disease that may be life-threatening when the muscles involved in breathing are affected.

What is the estimated number of patients affected by the condition?

At the time of designation, myasthenia gravis affected less than 2 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 101,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

What treatments are available?

At the time of designation, three medicines that reduce the breakdown of acetylcholine were authorised in the EU for the treatment of myasthenia gravis. Surgery to remove the thymus gland (thymectomy) was performed in some patients. Medicines that reduce the activity of the immune system, such as corticosteroids, were used in patients with disabling weakness, especially those who could not be treated or failed to respond to thymectomy. In patients with severe weakness causing breathing or swallowing problems, plasma exchange was used to remove the abnormal antibodies from the blood.

The sponsor has provided sufficient information to show that the medicine containing peptides mimicking antigen receptors on autoimmune B cells and autoimmune T cells associated with myasthenia gravis might be of significant benefit for patients with myasthenia gravis because early studies in experimental models indicate that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

The medicine containing peptides mimicking antigen receptors on autoimmune B cells and autoimmune T cells associated with myasthenia gravis works as a vaccine. It contains peptides (protein fragments) that are designed to activate the patient’s immune system so that it attacks and blocks the activity of the abnormal antibodies that damage acetylcholine receptors. By helping to reduce the damage to these receptors, this medicine is expected to improve muscle contraction and relieve the symptoms of patients with myasthenia gravis.

What is the stage of development of this medicine?

The effects of the medicine containing peptides mimicking antigen receptors on autoimmune B cells and autoimmune T cells associated with myasthenia gravis have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials in patients with myasthenia gravis had been started.
At the time of submission, this medicine was not authorised anywhere in the EU for myasthenia gravis or designated as orphan medicinal product elsewhere for this condition.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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 a marketing authorisation.