EU/3/08/539 - orphan designation for treatment of Wilson's disease

ammonium tetrathiomolybdate

Overview

On 1 April 2008, orphan designation (EU/3/08/539) was granted by the European Commission to JJGConsultancy Ltd, United Kingdom, for ammonium tetrathiomolybdate for the treatment of Wilson's disease.

What is Wilson's disease?

Wilson's disease is a genetic disorder that causes excessive copper accumulation in the body, typically in the liver and 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's disease, the copper that is normally 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.

What are the methods of treatment available?

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

Ammonium tetrathiomolybdate might be of potential significant benefit for the treatment of Wilson's disease, because it is expected to be beneficial for the patients with Wilson's disease who suffer from neurological symptoms. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

What is the estimated number of patients with Wilson's disease*?

Based on the information provided by the sponsor and previous knowledge of the Committee, Wilson's disease was considered to affect not more than 0.6 in 10,000 persons in the European Union which, at the time of designation, corresponded to about 30,000 persons.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Ammonium tetrathiomolybdate binds to copper and to a protein called albumin in the bloodstream. Once bound to ammonium tetrathiomolybdate and albumin, copper cannot be taken up by the organs and the damaging effects of copper are expected to decrease. Ammonium tetrathiomolybdate also acts in the intestine, by blocking the absorption of copper into the bloodstream, then decreasing copper uptake.

What is the stage of development of this medicinal product?

The effects of ammonium tetrathiomolybdate were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with Wilson's disease were ongoing.

Ammonium tetrathiomolybdate was not authorised anywhere worldwide for Wilson's disease, at the time of submission. Orphan designation of ammonium tetrathiomolybdate was granted in the United States for the treatment of Wilson's disease.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 February 2008 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• 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.

EU/3/08/539: Public summary of positive opinion for orphan designation of ammonium tetrathiomolybdate for the treatment of Wilson’s disease

Adopted Reference Number: EMEA/COMP/82161/2008

Key facts

• Active substance:
  ammonium tetrathiomolybdate
• Intended use:
  Treatment of Wilson's disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/08/539
• Date of designation:
  01/04/2008
• Sponsor:

  JJGConsultancy Ltd; Evercreech House; Evercreech, Somerset; BA4 6HZ; United Kingdom; Telephone: + 44 1749 838 886; Telefax: + 44 1749 838 887; E-mail: [e-mail]