On 26 October 2018, orphan designation (EU/3/18/2076) was granted by the European Commission to Orphan Europe SARL, France, for glycine, L-alanine, L-arginine, L-aspartic acid, L-cysteine, L-glutamic acid, L-histidine, L-lysine monohydrate, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, taurine for the treatment of maple syrup urine disease.
Maple syrup urine disease is an inherited disorder in which patients are unable to break down ‘branched chain amino acids’ or BCAAs which are found in some proteins. As a result, BCAAs build up to toxic levels in the body, particularly in the brain where they can lead to brain damage.
The most severe forms of the disease are present at birth and symptoms include delayed development, behavioural problems and learning disability. Infections or other illness, stresses such as surgery or excess dietary protein may induce severe attacks leading to seizures (fits), swelling and fluid build-up in the brain and coma.
Maple syrup urine disease is a long-term debilitating and life-threatening disorder due to its effects on normal development and damage to the brain.
At the time of designation, maple syrup urine disease affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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 517,400,000 (Eurostat 2018).
At the time of designation, no suitable treatments were authorised in the EU for maple syrup urine disease. Patients were managed with strict diets to control the amount of BCAAs taken in from proteins. Some forms of the disorder also responded to B vitamin supplements.
Some patients needed to be treated in hospital to be fed via a tube or drip with BCAA-free solutions, or procedures to filter BCAAs directly from the blood. Some patients may be suitable for liver transplantation, which restores the ability to break down BCAAs.
The medicine consists of a solution of amino acids (substances that make up proteins) but does not contain any BCAAs. The amino acids are to be given by infusion (drip) into a vein to replace other sources of amino acids. The amino acids are expected to be used by the body to make proteins together with excess BCAAs that have built up because of the disease. This is expected to reduce the level of BCAAs in the body, thereby controlling symptoms of the disease.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with maple syrup urine disease were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for maple syrup urine disease 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 13 September 2018 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.
Recordati Rare Diseases
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: