EU/3/03/163 - orphan designation for treatment of hyperphenylalaninaemia
5,6,7,8-Tetrahydrobiopterin
OrphanHuman
Overview
On 2 October 2003, orphan designation (EU/3/03/163) was granted by the European Commission to Prof. Dr. A. A. Roscher, Germany, for 5,6,7,8 tetrahydrobiopterin for the treatment of hyperphenylalaninemia.
The sponsorship was transferred to Orphanetics Pharma Entwicklungs GmbH, Austria, in December 2005.
Hyperphenylalaninemia or phenylketonuria, is a congenital disease (due to a genetic abnormality) and is caused by a reduced activity of an enzyme, phenylalanine hydroxylase. This enzyme is responsible to convert a certain aminoacid (a building block for a protein) called phenylalanine, into another aminoacid called tyrosine. The result is an accumulation of phenylalanine in the blood (and urine), which is toxic at high levels and can lead to severe brain damage. The disease is subdivided into mild, moderate and severe forms, according to the degree of elevation of these blood levels.
Hyperphenylalaninemia is a chronically debilitating and is characterised by mental retardation if left untreated.
At the time of submission of the application for orphan drug designation, the treatment of hyperphenylalaninemia consisted of lifelong dietary protein restriction, in other terms a low phenylalanine diet.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product might be of potential significant benefit for the treatment of hyperphenylalaninemia, particularly in terms of improved tolerance to phenylalanine dietary intake. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.
According to the information provided by the sponsor, hyperphenylalaninemia was considered to affect about 64,000 persons in the European Union.
*Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 385,000,000 (Eurostat 2002) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.
Tetrahydrobiopterin might help to restore the phenylalanine hydroxylase enzyme activity. As a result more phenylalanine might be converted to tyrosine, hence decreasing the toxic level.
The evaluation of the effects of 5,6,7,8 tetrahydrobiopterin in experimental models is ongoing.
At the time of submission of the application for orphan designation, clinical trials in patients with hyperphenylalaninemia were ongoing.
The medicinal product was not marketed anywhere worldwide for hyperphenylalaninemia or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 30 July 2003 a positive opinion recommending the grant of the above-mentioned designation.
- the seriousness of the condition,
- the existence or not of alternative methods of diagnosis, prevention or treatment and
- either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.
Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.
Key facts
- Active substance
- 5,6,7,8-Tetrahydrobiopterin
- Intended use
- Treatment of hyperphenylalaninaemia
- Orphan designation status
- Positive
- EU designation number
- EU/3/03/163
- Date of designation
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:
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: