EU/3/15/1471: Orphan designation for the treatment of Wilson's disease

Wilson's disease is a genetic disorder that causes copper absorbed from food to accumulate in the body. In healthy people, liver cells remove most of the excess copper and release it into the bile, which flows into the intestines. In people with Wilson's disease, due to a genetic defect, the liver cannot remove copper and the copper builds up in the liver and in other organs such as the kidneys, brain and eyes, and damages them.

Wilson's disease is chronically debilitating and can be life threatening if not treated due to the toxicity of copper in the liver and brain.

At the time of designation, Wilson's disease affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 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 512,900,000 (Eurostat 2015).

At the time of designation, several medicines were authorised in the EU for the treatment of Wilson's disease, including penicillamine and trientine dihydrochloride, which is used in patients who cannot tolerate penicillamine but is only authorised in one EU country. These medicines were used to remove excess copper from the body and to limit the absorption of further copper from food. Zinc acetate was also authorised for Wilson's disease, although it was not recommended for use at the beginning of treatment.

The sponsor has provided sufficient information to show that trientine tetrahydrochloride might be of significant benefit for patients with Wilson's disease because it is assumed to be similar to trientine dihydrochloride and an orphan designation may encourage it to be made more widely available. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Trientine tetrahydrochloride is expected to work in the same way as trientine dihydrochloride, by attaching to the free copper in the body and forming a compound that can be excreted in the urine by the kidneys.

The effects of trientine tetrahydrochloride have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with trientine tetrahydrochloride had been started.

At the time of submission, trientine tetrahydrochloride was not authorised anywhere in the EU for Wilson's 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 12 February 2015 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.