EU/3/00/012: Orphan designation for the treatment of tyrosinaemia type 1

Tyrosinaemia is an inborn error of metabolism, in which the body cannot effectively break down the amino acid (building blocks of proteins in our body) tyrosine. There are three types of tyrosinaemia, each with distinctive symptoms and caused by the deficiency of a different enzyme (a protein that can trigger a chemical reaction in the body). Patients with tyrosinaemia type 1 are born with a defective gene coding for an enzyme called 4-hydroxyphenylpyruvate oxidase. Normally this enzyme breaks down tyrosine. Since tyrosine is not properly broken down by the body, harmful substances build up in the body. This results in damage to the liver and kidneys. Untreated, tyrosinaemia type 1 is chronically debilitating and life-threatening.

At the time of designation, tyrosinaemia type 1 affected not more than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 3,800 people*, and is below the threshold 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. At the time of designation, this represented a population of 375,500,000 (Eurostat 2000).

No medicinal products were authorised for the treatment of tyrosinaemia type 1 in the Community at the time of submission of the application for orphan-drug designation. The therapy included a special diet and symptomatic treatment.

Nitisinone blocks the breakdown of tyrosine before it can be transformed into harmful substances. According to the sponsor, nitisinone is expected to limit the liver and kidney damages seen in patients with the condition.

The effects of nitisinone were evaluated in experimental models. At the time of submission of the application for orphan designation, a clinical trial in patients with tyrosinaemia type 1 was ongoing.

Nitisinone was not marketed anywhere worldwide for the treatment of tyrosinaemia type 1, at the time of submission. Orphan designation of nitisinone was granted in the United States in May 1995 for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 27 October 2000 recommending the granting of this designation.

Update: Nitisone (Orfadin) was designated as an orphan drug in Australia in October 2008 for the condition.

Nitisinone (Orfadin) was authorised in the EU on 21 February 2005 for treatment of patients with confirmed diagnosis of hereditary tyrosinaemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.