On 21 May 2015, orphan designation (EU/3/15/1489) was granted by the European Commission to Toleranzia AB, Sweden, for fusion proteins composed by a genetically modified cholera toxin subunit A1, peptides from the acetylcholine receptor alpha chain and a dimer of the D fragment from Staphylococcus aureus protein A for the treatment of myasthenia gravis.
Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in April 2019 on request of the Sponsor.
Myasthenia gravis is a disease that leads to muscle weakness and tiredness. It is an autoimmune 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 drop. 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 approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 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. This represents a population of 512,900,000 (Eurostat 2015).
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 this medicine might be of significant benefit for patients with myasthenia gravis because experimental studies show that it can help improve muscle function. In addition, it acts in a different way to existing treatments and might be able to be used in combination with them. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine is made up of three protein fragments linked together. One of these fragments is a part of the acetylcholine receptor and it works by inducing immune system tolerance to the acetylcholine receptors. When given to the patient, the medicine is expected to help prevent the immune system from attacking acetylcholine receptors, thereby reducing damage to acetylcholine receptors and helping to control the disease.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with myasthenia gravis had been started.
At the time of submission, the medicine 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 16 April 2015 recommending the granting of this designation.
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.
Toleranzia AB
Arvid Wallgrens backe 20, 8th floor
413 46 Goteborg
Sweden
Tel. +46 704 566 441
Fax +46 317 865 150
E-mail: martina.verolin@toleranzia.com
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: