ASAQ: Contribution of DNDi and FACT Partners Rationale for AS+AQ in Africa
In 1998, the UNICEF-UNDP-World Bank-WHO’s Special Programme for Research and Training in Tropical Diseases (TDR) was charged by the US Agency for International Development and the Wellcome Trust with the task of identifying suitable combinations of existing antimalarial drugs to control malaria resistance. From their data analyses, it emerged that AS+AQ could be a good clinical option in many parts of Africa.
In 2001 the World Health Organization recommended, in particular, the use of four artemisinin-based combination therapies (ACTs), including the combination of AS+AQ. However, in the case of AS+AQ, there was neither a co-formulation nor any development partners.
FACT Project: ASAQ, 2002-2009
FACT 2002-2006 : ASAQ Development through Registration
The FACT (Fixed-Dose Artesunate Combination Therapy) project began in 2002, under the umbrella of MSF (and then DNDi) in coordination with TDR.
- Objective: to develop a fixed-dose combination of AS+AQ for international registration that would improve compliance and would be available to all countries where resistance to amodiaquine was low (mainly African countries, but also some Asian countries like India and Indonesia)
- Key partners (who signed onto the original EU INCO-DEV grant): Instituto de Tecnologia em Farmacos of Farmanguinhos, Mahidol University, Université Victor Segalen Bordeaux 2 (TROPIVAL), University of Oxford, University Sains Malaysia, Centre National de Recherche et de Formation sur le Paludisme (CNRFP).
| Development Step | Institutions Involved |
| Pharmaceutical and Preclinical Development |
| Vital to the efforts of the FACT Project throughout the entire period of development has been the contribution and expert advice of academics | University of Oxford (UK)
Mahidol University (Thailand) |
| Preformulation, coordination and local support with partners in Bordeaux region | Tropival of Univ Bordeaux II (France) |
Formulation of combination product adapted with appropriate stability and biopharmaceutical characteristics and with a viable manufacturing process
Development and validation of analytical methods
First scale up coordinated with Rottendorf Pharma | Ellipse Pharma (France) |
| Set of GLP toxicology studies on single drugs and combinations | Unitox and Genotox (Brazil) |
| Development and utilization of toxico-kinetic protocols, bioanalytical methods | University Sains Malaysia (USM) (Malaysia) |
| First industrial scale up and GMP production of the FDC for clinical and stability studies | Rottendorf Pharma (Germany)
Creapharm (France) |
| Innovative partnership signed with industrial partner | sanofi-aventis: Contract signed, Dec 2004 |
| Clinical Development |
| Phase I for PK data, biopharmaceutical quality, and bioavailability | University Sains Malaysia (Malaysia) |
| Field-based Phase III to examine efficacy and tolerability of ASAQ vs non-fixed AS+AQ in children <5 years of age | Cardinal Systems (France)
CNRFP (Burkina Faso) |
| Support of 10-year survey of efficacy, tolerability, and pharmacovigilance in Senegal | Institut de Recherche pour le Développement (IRD) (Senegal)
Ministère français des Affaires Etrangères (FAC 2000 programme)
Ministère français de la Recherche (PAL+), TDR.
As of 2007: Ongoing in year 7 |
| Support of meta-analysis of 31 clinical studies examining AS+AQ vs other antimalarials | TDR with FACT partners, MSF/Epicentre |
FACT 2007-2009: Post-Registration Activities
Through 2009, DNDi intends to play an active role in facilitating FACT implementation by engaging partners that include pharmaceutical companies, national malaria programs, research institutes, contract research organisations, WHO, TDR, and NGOs.
DNDi has convened an independent panel of experts, the FACT Implementation Advisory Group, to provide independent advice and critical guidance about issues related to AS/AQ implementation and to advise on issues related to the rational use and towards ensuring equitable access.
| Illustrations of the Next Steps | Institutions Involved |
| Clinical study that will serve to facilitate the adoption of a new antimalarial policy | ICMR (India); sanofi-aventis (drug supply) |
| Workshop meeting to engage national malaria control program managers and international & regional organizations | KEMRI (Kenya) 30 (including NMCPMs, WHO, MMV, etc) attended meeting in Nairobi, Sept 2006. |
| Tolerability study | Epicentre / MSF, sanofi-aventis |
FACT Project: Resources 2002 - 2009
For the DNDi FACT Project, valuable in-kind contributions have supplemented the total budgetary costs of ASAQ covered by partners shown below.
6.4 Million Euros from Public and Private Resources
Allocated for ASAQ, 2002-2009
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