EU/3/14/1379 - orphan designation for treatment of malignant hyperthermia
Dantrolene sodium
OrphanHuman
Overview
On 19 November 2014, orphan designation (EU/3/14/1379) was granted by the European Commission to Eagle Laboratories Ltd, United Kingdom, for dantrolene sodium for the treatment of malignant hyperthermia.
The sponsorship was transferred to Maxia Strategies-Europe Limited, Ireland, in March 2019.
Malignant hyperthermia is an inherited disorder marked by rapid, uncontrolled muscle contractions and a rise in body temperature.
Symptoms can be triggered by certain medicines such as some general anaesthetics or the muscle relaxant succinylcholine, which cause the sudden release of abnormally high amounts of calcium within muscle cells. The release of calcium then makes the muscles to contract uncontrollably, leading to high body temperature, and other problems such as a rapid heart rate and muscle breakdown.
Malignant hyperthermia is a life-threatening condition due to heart arrhythmias (irregular heart beat), acidosis (high blood levels of acid) and muscle rigidity.
At the time of designation, malignant hyperthermia affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 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. This represents a population of 511,100,000 (Eurostat 2014).
At the time of designation, dantrolene sodium given by injection was already authorised in the EU for the treatment of malignant hyperthermia. However, the medicine was formulated in a way that does not allow the medicine to be given quickly in an emergency situation.
The sponsor has provided sufficient information to show that this medicine is a new formulation of dantrolene sodium which might be of significant benefit for patients with malignant hyperthermia because it is expected to be given quickly to patients with malignant hyperthermia thereby reducing morbidity and mortality associated with treatment delay. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
Dantrolene is a muscle relaxant that decreases the release of calcium from within muscle cells, helping the muscles to relax again.
It is expected that the new formulation will allow for a faster preparation of the medicine, as well as for a lower volume to be given to patients, which would allow for the medicine to be given without delay.
The effects of dantrolene sodium have been evaluated in experimental models.
At the time of submission of the application for orphan designation, a clinical trial with the new formulation of dantrolene sodium in healthy volunteers had finished and no further studies were planned.
At the time of submission, this medicine was not authorised anywhere in the EU for malignant hyperthermia. The medicine has received orphan designation and has been approved in the United States for malignant hyperthermia.
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.
- 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.
Key facts
- Active substance
- Dantrolene sodium
- Intended use
- Treatment of malignant hyperthermia
- Orphan designation status
- Positive
- EU designation number
- EU/3/14/1379
- Date of designation
- Sponsor
Maxia Strategies-Europe Limited
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
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.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: