EU/3/14/1353

On 19 November 2014, orphan designation (EU/3/14/1353) was granted by the European Commission to Temmler Pharma GmbH & Co. KG , Germany, for mexiletine hydrochloride for the treatment of myotonic disorders.

The sponsorship was transferred to Hormosan Pharma GmbH, Germany, in October 2015.

What are myotonic disorders?

Myotonic disorders are a group of inherited muscle disorders where muscles are slow to relax after contraction. The slow relaxation of the muscles causes symptoms such as stiffness and pain.

Myotonic disorders are caused by abnormalities in the ion channels, tiny pores in the muscle cells that control the passage of charged particles (ions) such as sodium or chloride and play a key role in the contraction and relaxation of muscles. When a muscle is affected by a myotonic disorder, these ion channels do not function properly. This dysfunction affects the ability of a muscle to relax after it has contracted. Until relaxation can properly occur, the muscles remain stiff and unusable.

Myotonic disorders are long-term debilitating conditions due to the pain and muscle stiffness, which are associated with frequent falls and disability.

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

At the time of designation, myotonic disorders affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 102,000 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).

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*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 511,100,000 (Eurostat 2014).

What treatments are available?

At the time of the orphan designation, mexiletine hydrochloride was authorised in France to treat myotonic disorders.

The sponsor has provided sufficient information to show that mexiletine hydrochloride might be of significant benefit for patients with myotonic disorders since the orphan designation may encourage it to be made more widely available. 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?

Mexiletine hydrochloride is a known antiarrhythmic medicine (used to restore normal heart rhythm). It works by blocking ion channels for sodium ions in muscle cells. These sodium channels play a role in the contraction and relaxation of muscles and by blocking them, the medicine helps to reduce the rate of contractions as well as the stiffness that occurs when the contractions are prolonged.

What is the stage of development of this medicine?

The effects of mexiletine hydrochloride have been evaluated in experimental models and in patients.

At the time of submission of the application for orphan designation, mexiletine hydrochloride was authorised in France for myotonic disorders. Orphan designations of mexiletine hydrochloride medicines have been granted in the EU and the United States for myotonic disorders.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.