EU/3/19/2187: Orphan designation for the treatment of myasthenia gravis

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 targets called acetylcholine receptors on 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 cannot contract normally. 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 approximately 1.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 88,000 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 518,400,000 (Eurostat 2019).

At the time of designation, several medicines were authorised in the EU for the treatment of myasthenia gravis, including acetylcholine esterase inhibitors (medicines that prevent breakdown of acetylcholine) and medicines that work on the immune system. Surgery to remove the thymus gland (thymectomy) was performed in some patients.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with myasthenia gravis because laboratory studies have shown that it slowed down worsening of the disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The active substance in the medicine is a protein similar to a part of the acetylcholine receptor but, unlike the natural receptor, it is not active. Cells of the immune system (the body's defences) adjust to accept the medicine without attacking it. As a result, it is thought that these cells will also accept the very similar natural acetylcholine receptors. Giving the medicine to patients is therefore expected to stop the immune system from attacking natural acetylcholine receptors and slow down worsening of the disease.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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 the treatment of myasthenia gravis. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 20 June 2019, 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.