Frequently asked questions about Eurartesim®

Dihydroartemisinin-piperaquine (Eurartesim®)is a novel combination therapy based on an artemisinin derivative extracted from Artemisia Annua, a traditional Chinese medicinal treatment for “fever", and an antimalarial drug, piperaquine, which remains in the body for up to 60 days. Eurartesim has proved effective in the treatment of uncomplicated Plasmodium falciparum malaria. It has been evaluated in clinical trials in adults, children and infants of 6 months and over.

 

What is it?

Eurartesimis a new treatment in theArtemisinin-based Combination Therapy (ACT) drug class. ACTs are antimalarial treatments which combine, in the same tablet, an artemisinin derivative — highly effective but eliminated from the body in just a few hours — with another antimalarial drug which in contrast is eliminated very slowly. The combination of two antimalarial compounds also helps prevent the emergence of resistance to both drugs.

In comparison with other antimalarial treatments on the market in Europe and in countries where malaria is endemic, dihydroartemisinin-piperaquine not only requires a simpler dosage scheme (once a day for 3 days) but also has a greater capacity to protect patients against new infections. In fact, piperaquine remains in the body at effective concentrations for about 60 days after the last administration.

 

How was it developed?

The project for the development and registration of dihydroartemisinin-piperaquine began in 2004, through the partnership of Sigma-Tau, Italy, the University of Oxford and Medicines for Malaria Venture (MMV), Geneva, a leading not-for-profit organisation established in 1999 to boost the research and development of new antimalarial drugs. MMV receives funding from numerous donors, including the Bill & Melinda Gates Foundation. The aim of the partnership was to achieve market authorisation for Eurartesim, first in Europe, followed by WHO Prequalification and introduction in malaria endemic countries. Registration with the European Medicines Agency (EMA) provides an assurance that the drug has been developed and manufactured to high-quality standards.

The WHO has been kept constantly up-to-date on the progress of Eurartesim development.

 

How does it work?

Dihydroartemisinin kills the plasmodia parasites, destroying their mitochondrial and nuclear membranes through the production of free radicals, while piperaquine blocks the digestion of haemoglobin, which the parasite feeds upon.

Dihydroartemisinin-piperaquine kills the parasites quickly, producing a fast resolution of clinical signs and symptoms. Treatment is complete in just 3 days.

For patients (whether local or travellers) treated in countries in which malaria is endemic, the slow clearance of piperaquine prevents new infections for 40-60 days.

 

Treatment and dosage

Dihydroartemisinin-piperaquine (DHA/PQP) is administered once a day for 3 consecutive days. The dosage (quantity and number of tablets) to be taken in each administration depends on the patient's body weight.

Two different packs with different quantities of the active ingredients in the tablets are available: 20 mg of DHA and 160 mg of PQP; 40 mg of DHA and 320 mg of PQP.

Tablets must be taken between meals with a little water. Tablets may be crushed and diluted in a little water for children who are unable to swallow them. A new paediatric formulation (water-dispersible tablets) is in development.

 

Tolerance profile

Dihydroartemisinin-piperaquine is generally well tolerated. Its safety has been evaluated in two open-label studies in which it was used to treat 1,239 paediatric patients aged up to 18 years and 566 adults aged over 18 years.

Side-effects were found to be mild and generally not serious. These included coughing, fever, headache, anaemia, asthenia, anorexia and changes in blood cell parameters similar to those seen in the acute phase of malaria.

 

Studies supporting European registration

The efficacy of dihydroartemisinin-piperaquine has been confirmed by various clinical trials conducted by Sigma-Tau and involving over 2,700 patients in Africa (Burkina Faso, Zambia, Kenya, Mozambique and Uganda) and Asia (Thailand, India and Laos). These included 1,600 children under the age of 5 years. The drugs used as comparators were artemether-lumefantrine in Africa and artesunate + mefloquine in Asia, both Artemisinin-based Combination Therapies (ACTs). Around 95% of patients were malaria-free when tested 7 days after the start of the treatment as well as after 28 days. These tests were done to exclude cases of recrudescence due to parasite resistance.

In addition to the studies conducted directly by Sigma-Tau for registration purposes, many other non-sponsored trials have been conducted by independent investigators. These have involved around 9,000 patients treated with dihydroartemisinin-piperaquine and a similar number treated with comparator medicines. The efficacy and safety seen in these clinical studies were similar to those found in trials conducted directly by Sigma-Tau.