EU/3/07/468: Orphan designation for the treatment of 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 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. 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 hospitalization.

At the time of designation, malaria was considered to affect approximately 0.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 15,000 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 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.

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 the combination of dihydroartemisin and piperaquine might be of potential significant benefit for the treatment of malaria, mainly because it might improve survival in those suffering severe, life-threatening malaria. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Dihydroartemisin is the active form of artesunate, 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.

Piperaquine is a chemical compound related to chloroquine, a product extensively used in the treatment of malaria. Its mechanism of action is based on the inhibition of the detoxification by the Plasmodium of heme molecules that accumulate in the parasite.

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

Dihydroartemisin, piperaquine was not authorised anywhere worldwide for malaria, at the time of submission. Orphan designation of dihydroartemisin, piperaquine was granted in the United States for malaria.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 25 June 2007 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.