EU/3/07/510

On 6 December 2007, orphan designation (EU/3/07/510) was granted by the European Commission to Sigma-tau Pharma UK, United Kingdom, for artesunate for the treatment of malaria.

The sponsorship was transferred to Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Italy, in April 2012.

What is malaria?

Malaria is an infectious disease caused by Plasmodium parasites. There are four species of Plasmodium that may infect humans: P. vivax, P. malariae, P. ovale and P. falciparum. Malaria is carried from person to person by infected Anopheles mosquitoes, and transmission occurs mostly in tropical and subtropical regions including parts of the Americas, Asia, and Africa. In Europe, malaria is mainly encountered in travellers returning from these areas. Following a bite from an infected mosquito, the parasite goes to the liver. When the parasite then enters the bloodstream it infects and destroys red blood cells.

Fever is the major symptom of malaria. The disease must always be suspected when fever occurs during or after travel to an infected area. In addition, flu-like symptoms such as chills, headaches, muscle-aches, and fatigue can occur. Malaria due to P. falciparum may progress rapidly causing seizures, coma, breathing and kidney problems. The disease is life-threatening, and active malaria infection with P. falciparum is a medical emergency requiring hospitalisation.

What is the estimated number of patients affected by the condition?

At the time of designation, malaria affected approximately 0.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 15,189 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. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

Several medicinal products with anti-malarial activity were authorised for the condition in the Community at the time of submission of the application for orphan drug designation.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that artesunate might be of potential significant benefit for the treatment of malaria, mainly because it might improve survival in those suffering severe, life-threatening malaria.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Artesunate is a chemically modified derivative of the natural product artemisinin, which is found in sweet wormwood. It is proposed that it acts by damaging the membrane of the parasite, thus killing the parasite.

What is the stage of development of this medicine?

The effects of artesunate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with malaria were ongoing.

At the time of submission of the application for orphan designation, artesunate was not authorised in the European Union.

Orphan designation of intravenously administered artesunate had been granted in the United States for immediate treatment of malaria.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 October 2007 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria

• 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