EU/3/14/1304

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Orphan designation

On 29 July 2014, orphan designation (EU/3/14/1304) was granted by the European Commission to Alexion Europe SAS, France, for eculizumab for the treatment of myasthenia gravis.

Eculizumab in treatment myasthenia gravis in has been authorised in the EU as Soliris since 14 August 2017.

What is myasthenia gravis?

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.

What is the estimated number of patients?

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 isbased 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).

What treatments are available?

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

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

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 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.

Name Language First published Last updated
EU/3/14/1304: Public summary of opinion on orphan designation: Eculizumab for the treatment myasthenia gravis (English only) 2014-09-01 2015-03-25

Key facts

Product details for <p>Eculizumab</p>
Active substanceEculizumab
Medicine NameSoliris
Disease/conditionTreatment myasthenia gravis
Date of decision29/07/2014
OutcomePositive
Orphan decision numberEU/3/14/1304

Review of designation

On 3 July 2017, the Committee for Orphan Medicinal Products (COMP) concluded its review of the designation EU/3/14/1304 for Soliris (eculizumab) as an orphan medicinal product for the treatment of myasthenia gravis. The COMP assessed whether, at the time of addition of a new indication to the marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with myasthenia gravis. The COMP recommended that the orphan designation of the medicine be maintained.1


1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended extending the approved therapeutic indication for Soliris to include the following indication in adults:

‘treatment of refractory generalised myasthenia gravis in patients who are anti-acetylcholine receptor antibody-positive’.

This falls within the scope of the product’s designated orphan indication, which is ‘treatment of myasthenia gravis’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2014. Myasthenia gravis remains a condition that is long-term debilitating and life threatening due to the weakening of the breathing muscles.

Prevalence of the condition

Following a review of the scientific literature, the sponsor provided an updated estimate of the prevalence of myasthenia gravis, which has increased due to greater awareness and detection of the condition.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of myasthenia gravis remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 3.7 people in 10,000. This is equivalent to a total of around 191,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of myasthenia gravis. They included medicines called acetylcholinesterase inhibitors, corticosteroids and medicines that reduce the activity of the immune system (the body’s natural defences).

Significant benefit of Soliris

The COMP concluded that the claim of a significant benefit of Soliris in myasthenia gravis is justified because the medicine has been shown to improve symptoms when added to standard treatment in patients whose disease did not respond to at least one previous treatment.

This is based on a study in patients whose disease did not respond to at least one other treatment considered best standard of care such as corticosteroids, immunosuppressant medicines and acetylcholinesterase inhibitors. The majority of patients were also receiving background therapy with a standard treatment. The results showed that treatment with Soliris led to an additional improvement of patients’ symptoms and ability to carry out daily activities.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Soliris is of significant benefit to patients affected by myasthenia gravis.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Soliris still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

More information on the COMP assessment can be found in the July 2017 COMP minutes.

Further information on Soliris can be found in the European public assessment report (EPAR) on the Agency’s website.

Sponsor’s contact details

Alexion Europe SAS
1-15, avenue Edouard Belin
92500 Rueil-Malmaison
France
Tel. +33 1 47 32 36 21
Fax +33 1 47 10 24 46
E-mail: medicalinformation.europe@alxn.com

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.