One of the first medicines developed by Drugs for Neglected Diseases Initiative (DNDi), fixed-dose artesunate-mefloquine will be easier to use and less expensive than current ACTs, but experts agree that action is needed to make sure the treatments reach patients.

The new, non-patented malaria treatment, artesunate-mefloquine, will be available in the global fight against the disease by the summer of  2007, DNDi announced today at the Prince Mahidol Award Conference. Earlier in the week, experts from ministries of health and non-governmental organizations from 9 Asian countries met to discuss how to engender greater regional partnership in ACT implementation and clinical research.

The fixed-dose, artemisinin-based combination therapy (ACTs), artesunate/mefloquine (AS/MQ)is an easy-to-use and effective innovation that ensures that the drugs are taken together and in correct proportions and that is designed to improve treatment compliance by offering both a paediatric strength as well as fewer tablets in the treatment regimen. Most of the patients on the new treatment will need to take just one tablet a day for three days.

The product, which will be made available as a public good so that it reaches the greatest number of patients, is the fruit of a unique partnership between DNDi; the Brazilian public pharmaceutical company, Farmanguinhos; and the Indian generic pharmaceutical company, Cipla. The fact that the drug will not be under patent removes a significant barrier to availability and should serve as a model for future drug development for neglected diseases

Begun in 2002, DNDi’s innovative FACT Project (fixed-dose, artemisinin-based combination therapy) has brought together academic, public and private partners from around the world to address the need for more effective tools to battle malaria.

“This new fixed-dose combination has been adapted to patients’ needs in that AS/MQ is more affordable and easier to use,” said Dr. Bernard Pecoul, Executive Director of DNDi. “But it is important that we move forward, in partnership with regional experts and authorities, to ensure that AS/MQ reaches the patients who are desperately in need.”
Because increasing resistance has rendered common anti-malarials like chloroquine ineffective, the World Health Organization (WHO) has recommended the use of ACTs since 2001. However, high cost and procurement problems on the local and regional have so far prevented wider access to ACTs. A major discussion point at today’s briefing was the cost of DNDi’s new AS/MQ formulation being US$2-$2.50 US for adults and US$1-$1.50 US for children.

“We have to find ways to make the price of these new medicines, and ACTs in general, comparable to the cost of chloroquine,” said Professor Nick White, Professor of Tropical Medicine at Oxford University. “A subsidized fund could be one solution, but it is clear that the international community has to take immediate steps to fund the fight against malaria with medicines that work.”

For further information, or to arrange interviews with Dr Nick White and Dr Bernard Pecoul, please call Ann-Marie Sevcsik on +41 79 814 9147 amsevcsik@dndi.org

Drugs for Neglected Diseases initiative (DNDi) is a not-for-profit drug development initiative established in 2003 by five publicly-funded research organisations – Kenya Medical Research Institute, Indian Council of Medical Research, Oswaldo Cruz Foundation Brazil, Malaysian Ministry of Health, and the Institut Pasteur; an international research organisation WHO’s Tropical Diseases Research programme; and an international humanitarian organisation Médecins Sans Frontières.

• DNDi – whose primary aim is to develop 6-8 new, improved and field-relevant drugs by 2014 for neglected diseases such as malaria, visceral leishmaniasis, human African trypanosomiasis, and Chagas disease, that afflict the very poor in developing countries – also strengthens existing research capabilities in countries where neglected disease are endemic and advocates for increased priority and funding for research and development of drugs for neglected diseases.
  
  Global burden of malaria
• the most widespread of all transmissible diseases
• affects most tropical and sub-tropical countries in sub-Saharan Africa, South and South-East Asia, and South America, with one-third of the world population estimated to live in endemic areas
• every year, approximately 500 million people develop malaria and over 2 million people die
• 1 million children under the age of 5 die every year
• this translates to 3000 children every day, an astonishing 1 death every 30 seconds.

The Fixed-dose Artesunate-based Combination Therapies (FACT) project demonstrates the efficacy of partnerships in the field of drug R&D for neglected diseases.  Fast-track development, testing, and registration of the two FDCs, artesunate-amodiaquine (AS/AQ) and artesunate-mefloquine (AS/MQ), were the primary objectives of the project and are being achieved by the multi-partner FACT Project Consortium: DNDi; Tropival of the Bordeaux2 University, France; Oxford University’s Centre for Tropical Medicine University, UK; the Drug Research Centre at Universiti Sains Malaysia; Mahidol University’s Faculty of Tropical Medicine, Thailand; Instituto de Tecnologia em Fármacos (Farmanguinhos), Brasil; Tropical Disease Research Programme (TDR) in Switzerland; and the Centre National de Recherche et de Formation sur le Paludisme (CNRFP) in Burkina Faso. Partnering with pharmaceutical companies like sanofi-aventis was also essential for efficient industrialization, registration, and distribution of the new products.
DNDi initiated the FACT project for malaria in 2002, in association with Médecins Sans Frontières (MSF), the INCO-DEV programme of the European Union, and the UNICEF-UNDP-World Bank-WHO’s Special Programme for Research and Training in Tropical Diseases (WHO/TDR).  Consistent with DNDi’s mission of collaboration based on relative strengths, the FACT project capitalizes on the skills and know-how of a broad range of partners in both developing and developed countries. Thus far, the FACT project has received financial support from the European Union, Agence Française de Développement (AFD), the Swiss Development Cooperation, and the Dutch government.

How could AS/MQ be used?
Consistent with 2006 WHO treatment guidelines, AS/MQ will serve as a fixed-dose combination for the treatment of uncomplicated P.falciparum malaria in paediatric and non-pregnant adult populations.  Drug deployment efforts will initially focus on areas of low transmission, including Southeast Asia and South America, AS/MQ can potentially be used in all endemic regions including those affected by multi-drug resistant P.falciparum strains.

A Phase III clinical trial conducted in Thailand confirmed that the fixed-dose AS/MQ’s efficacy and side effect profile were equivalent to the loose formulation (Ashley et al. Trop Med Int Health. 2006). As such, the available evidence supports the deployment of fixed-dose AS/MQ as an alternative to the loose formulation.

How much will AS/MQ cost?
The target price is less than $2-2.5 per full adult treatment.

• What is the appropriate dosage and treatment regimen for AS/MQ?
• Fixed-dose oral combination (FDC) tablets.
• Two strengths: AS25+MQ55mg and AS100+MQ220mg.
• Dosing regimen: QD, 12 mg/kg AS and 24mg/kg MQ total dose over three days, based on age.
• Children
  What is the added value of AS/MQ?
  AS/MQ offers a fixed-dose combination for one of the world’s most effective treatments for malaria.  The simplicity of the treatment, once daily dosing for three days and reduced pill burden, will make patient adherence easier.  Furthermore, AS/MQ will be produced in a special pediatric formulation that will aid treatment of infants, children, and teenagers.