EU/3/03/172

Wilson's disease is a genetic disorder that causes excessive copper accumulation in the liver or brain. The liver of a person who has Wilson's disease does not release copper into the bile, as it should. Bile is a liquid produced by the liver that helps with digestion. In Wilson disease, the copper absorbed from the food by the intestines builds up in the liver and injures liver tissue. Eventually, the damage causes the liver to release the copper directly into the bloodstream, which carries the copper throughout the body. The copper accumulated and transported by the bloodstream can then cause damage in other organs like the kidneys, brain, and eyes. If not treated, Wilson's disease can be chronically debilitating and life threatening.

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 23,000 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 382,800,000 (Eurostat 2003).

Treatment of Wilson's disease generally consists of anti-copper agents to remove excess copper from the body and to prevent it from re-accumulating. Several medicinal products were authorised for Wilson's disease in the Community at the time of submission of the application for orphan drug designation.

Trientine dihydrochloride could be of potential significant benefit for the treatment of Wilson's disease, by making it available over the whole Community. In addition, trientine dihydrochloride may have a different safety profile for the treatment of the condition from that of medicinal products authorised today. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Trientine dihydrochloride binds to the free copper in blood and increases copper excretion in the urine. It might also act by blocking intestinal copper absorption, but this possible mechanism remains to be fully demonstrated.

The active substance, trientine dihydrochloride is authorised in the United Kingdom, in Wilson's patients who are intolerant of penicillamine therapy. The product authorised in the United Kingdom is exported to Germany, France, Greece, Norway, Switzerland, Austria and Ireland, however supply is restricted to named patients only.

Trientine dihydrochloride has been granted marketing authorisation in the United States for treatment of Wilson's disease in patients who are intolerant of penicillamine.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 September 2003 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 European Union) 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.