EU/3/09/702: Orphan designation for the treatment of malaria

Malaria is an infectious disease caused by Plasmodium parasites. There are four species of Plasmodium parasites that may infect humans: P. vivax, P. malariae, P. ovale and P. falciparum. They are transmitted from person to person by the bite of infected Anopheles mosquitoes. Once in the body, the parasites multiply in the liver and then infect and destroy red blood cells.

Transmission mostly occurs in tropical and subtropical regions including parts of the Americas, Asia, and Africa. In Europe, malaria mainly affects travellers returning from these areas.

Fever is the major symptom of malaria and 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 commonly occur.

Malaria is a severe and life-threatening disease because of its complications such as cerebral malaria (a deep coma caused by infected red blood cells adhering to blood vessels in the brain), seizures (fits), and breathing and kidney problems. Malaria due to P. falciparum is the most severe form and may rapidly lead to complications, especially in children and others with low immunity (protection) to the disease.

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 15,000 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 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 504,800,000 (Eurostat 2009).

At the time of designation, several medicines were authorised in the EU to treat malaria, including tablets containing a combination of beta-artemether and lumefantrine. This combination is a recommended option for non-complicated malaria, and is effective against malaria due to P. falciparum.

The sponsor has provided sufficient information to show that beta-artemether / lumefantrine (powder for oral suspension) might be of significant benefit for patients with malaria because of the way in which the medicine is given. This medicine is a powder to be made up into an oral suspension, which could be given to children and adults who have difficulty swallowing tablets. In addition, while for the authorised combination treatment four tablets need to be taken twice a day, the suspension is to be taken once a day. This might make it easier for patients to stick to their treatments. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Beta-artemether / lumefantrine (powder for oral suspension) contains two active substances, beta-artemether and lumefantrine, which are given together to improve effectiveness. The exact mode of action of these substances is not clear, but they are thought to work by damaging the membrane of the parasite, thus killing the parasite.

The effects of beta-artemether / lumefantrine (powder for oral suspension) have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the designated product in patients with malaria had finished.

At the time of submission, beta-artemether / lumefantrine (powder for oral suspension) was not authorised anywhere in the EU for malaria or designated as an orphan medicinal product elsewhere for this condition. The medicine was authorised outside the EU in 25 countries where malaria is endemic.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 November 2009 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 Community) 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.