EU/3/11/944: Orphan designation for the treatment of mercury toxicity

Mercury toxicity can occur when a patient has been exposed to mercury. The level of toxicity depends on the chemical form of the mercury and how the patient was exposed to it. Exposure may occur through certain foods (such as fish), from mercury-containing dental amalgams (a substance used in some dental fillings) or through contact with materials in factories where mercury-containing products are used or manufactured.

Mercury toxicity can lead to symptoms affecting several body systems such as the nervous, gastrointestinal (gut including the liver), and the renal (kidney) systems. Acute toxicity can result in shortness of breath, chest pain, chills, nausea and vomiting, joint swelling and rash, while long-term exposure to mercury commonly results in mouth lesions, tremor, poor coordination and psychiatric problems among others.

Mercury toxicity is life threatening due to the damage it can cause to the nervous, renal, endocrine (hormonal) and gastrointestinal systems.

At the time of designation, mercury toxicity affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

At the time of designation, medicines authorised in EU countries for mercury toxicity included dimercaptoprol, D-pencillamine, 2,3-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propane sulfonic acid (DMPS). These medicines are 'chelating' agents: they work by attaching to mercury to form a compound that can be more easily excreted from the body.

The sponsor has provided sufficient information to show that N,N'-bis(2-mercaptoethyl)isophthalamide might be of significant benefit for patients with mercury toxicity because it works in a partially different way to existing treatments and early studies indicate that it might improve the treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Like other medicines for mercury toxicity, N,N-bis-(2mercaptoethyl)isophthalamide is a chelating agent. However, while other medicines are 'hydrophilic', which means that they attach to the mercury found in water but not in fat, this medicine is 'lipophilic' and is expected to be able to reach the mercury in fatty tissues in the body. When the medicine is taken by mouth, it is expected to attach to the mercury in fatty tissues such as the brain, forming a compound which the body is then able to excrete.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with mercury toxicity had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for mercury toxicity 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 9 November 2011 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.