On March 1st 2007 the Drugs for Neglected Diseases initiative (DNDi) and Sanofi-Aventis are hosting a round table discussion to celebrate the availability of a new antimalarial treatment, the artesunate/amodiaquine fixed-dose ACT (ASAQ). We invited Jean-René Kiechel and Bernard Pecoul of DNDi to write a personal guest blog that explains why they think the availability of ASAQ is such a milestone.
Guest Blog: Innovative Partnership Brings New ACT Free of Patent, by Jean-René Kiechel & Bernard Pecoul
As the result of an innovative partnership between DNDI and sanofi-aventis, ASAQ, a new fixed-dose, antimalarial combination is now available for use throughout sub-Saharan Africa. This new drug, which has been adapted to patients’ needs, is safe, simple to use, affordable and a quality product. The fact that ASAQ is affordable right from the start and is not under patents removes a significant barrier to its availability and should serve as a model for future drug development for neglected diseases.
In 1998, the Special Programme for Research and Training on Tropical Diseases (TDR) investigated combinations of existing antimalarial drugs that might be suitable to control malaria resistance. From TDR’s analyses, it was clear that the combination of artesunate (AS) and amodiaquine (AQ) could be a good clinical option in many parts of Africa. In 2001, the WHO recommended the use of four Artemisinin-based Combination Therapies (ACTs), including the combination of AS and AQ. To date, of the 41 sub-Saharan countries that have adopted ACTs as their malarial treatment protocols, 20 have chosen the combination of AS and AQ.
In the case of AS and AQ in 2001, there was neither a co-formulation nor any development partners. As a result, the FACT (Fixed-Dose Artesunate Combination Therapy) project began in 2002, under the umbrella of MSF and then DNDi, in coordination with TDR. The project’s primary objective was to develop a fixed-dose combination of AS and AQ for 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).
DNDi has played an active role as a ‘virtual manager’ of many key partners involved, from pharmacological development (eg. Ellipse Pharma, initial developers of the stable co-formulation) through the pivotal phase III field study in Burkina Faso (eg. the Centre National de Recherche et de Formation sur le Paludisme, primary investigators of the trial) and through to industrial development and registration.
Since December 2004, DNDi and Sanofi-Aventis have been collaborating closely on industrial, preclinical and clinical product development to optimise the quality of ASAQ and to expedite its availability. DNDi has pursued the pharmaceutical and clinical investigations of the FACT programme, and sanofi-aventis has carried out numerous studies and the industrial scale-up and development. The drug has been registered since February 1st, 2007, in Morocco where the product is manufactured. Registration has been successfully completed in ten African countries and is ongoing in other endemic countries; sanofi-aventis has submitted a full dossier for WHO prequalification in February 2007.
High cost and procurement problems on local and regional levels have thus far prevented wider access to ACTs. In Africa, where malaria consumes 25% of household incomes and kills a child every 30 seconds, ASAQ offers a state-of-the art galenical formulation for all age groups with 3 different paediatric strengths (including for infants, the first ever for an ACT.) Patients are treated in a simple, one tablet once-a-day dosing regimen over the course of three days for children and two tablets once a day for adults.
For a full treatment cost of less than US$0.50 for children under 5 years old and less than US$1 for older children and adults, ASAQ will be available at cost to public organizations of endemic countries, international institutions, NGOs, and programs promoting access to drugs in pharmacies. Based on public sector and NGO experience, blister and box sizes were optimized to simplify management and storage.
ASAQ is innovative because it is: 1) Adapted to patient needs of all ages, from two well-known drugs, and to WHO recommendations; 2) Simple in terms of easy-to-use regimen, prescription, management and storage; 3) Accessible and available where it will be affordable and non-patented; and 4) Quality in terms of formulation, development, manufacturing and implementation.