EU/3/16/1682 - orphan designation for treatment of necrotising enterocolitis
melatonin
OrphanHuman
Overview
On 1 August 2016, orphan designation (EU/3/16/1682) was granted by the European Commission to Therapicon Srl, Italy, for melatonin for the treatment of necrotising enterocolitis.
The sponsor’s address was updated in August 2018.
The sponsorship was transferred to Worphmed Srl, Italy, in August 2018.
Necrotising enterocolitis is an inflammatory disease of the gut that affects preterm infants. In these infants, portions of the gut become inflamed and start to die. Symptoms may include problems with feeding, abdominal distension (bloating) and bloody stools. If the disease progresses, it can lead to tearing of the gut and the leakage of the contents of the gut into the abdomen causing peritonitis (infection of the abdominal cavity) and sepsis (infection of the blood).
Although the exact cause of necrotising enterocolitis is unclear, it is known that the gut and the immune system (the body's natural defence system) of preterm infants are immature and not as well developed as that of full term infants. In particular the intestinal flora, which consists of non-pathogenic (not causing disease) microorganisms that prevent the colonisation of pathogenic microorganisms in the gut, is altered, increasing the risk of injury and infection of the gut.
Necrotising enterocolitis is a severe and life-threatening disease that delays normal growth, causes malnutrition and can lead to complications such as gut perforation, sepsis and peritonitis.
At the time of designation, necrotising enterocolitis 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 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 513,700,000 (Eurostat 2016).
At the time of designation, there were no satisfactory methods authorised in the EU for the treatment of necrotising enterocolitis.
Melatonin is a natural substance produced in the body with a variety of activities. It is involved in controlling sleep patterns, it stimulates the production of many enzymes and acts as an antioxidant (a substance that helps the body protect itself against damage due to reactive substances containing oxygen). The exact way in which melatonin could work in necrotising enterocolitis is not clearly understood but it is thought that its ability to increase production of the enzyme heme oxygenase-1 may be important, since lack of this enzyme has been linked to necrotising enterocolitis. It is expected that, by increasing the amount of this enzyme, injections of melatonin may help reduce the symptoms of necrotising enterocolitis.
The effects of melatonin have been evaluated in experimental models.
At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with necrotising enterocolitis had been started.
At the time of submission, melatonin given by mouth as tablets was authorised in the EU for short-term treatment of insomnia.
At the time of submission, the medicine was not authorised anywhere in the EU for necrotising enterocolitis 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 19 May 2016 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
- melatonin
- Intended use
- Treatment of necrotising enterocolitis
- Orphan designation status
- Positive
- EU designation number
- EU/3/16/1682
- Date of designation
- Sponsor
Worphmed Srl
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: