Developed by DNDi and partners
2015 is the year the malaria community hoped to achieve universal coverage with existing interventions, near zero deaths, and a 75% reduction of global incidence from 2000 levels. The world is edging closer to these ambitious goals – malaria mortality rates fell by approximately 47% worldwide and incidence rates by 26%.
Tangible gains have been made in the fight against this terrible disease by increased prevention measures and improved case management using rapid diagnostic tests and quality artemisinin combination therapies. The 2014 World Malaria Report stated that in the 97 countries and territories with ongoing malaria transmission, 43,000 fewer people died in 2013 from malaria than in 2012. This is encouraging news. However, 584,000 people died of malaria in 2013; so, much still remains to be done if the lives of these vulnerable patients are to be saved.
The DNDi role
As part of these efforts to fight malaria, the Fixed-Dose Artesunate Combination Therapies (FACT) consortium was established in 2002 by the Drugs for Neglected Diseases Working Group of the MSF Access Campaign with WHO-TDR, and subsequently transferred to DNDi when it was established in 2003. FACT aimed to develop two fixed-dose artemisinin-based combination therapies (ACTs) associating artesunate (AS) with amodiaquine (AS) or mefloquine (MQ), two of the treatments recommended by the WHO in response to increasing chloroquine resistance, but that were not available in field-adapted fixed-dose formulations. These were to be easy-to-use formulations, suitable for both adults and children, affordable, stable in tropical conditions, and available on an unrestricted license as public goods. FACT pioneered innovative approaches to drug development, working with the pharmaceutical industry, start-ups, academia, NGOs, national control programmes, and other partners through its flexible, ‘virtual’ model.
ACTs developed as public health goods
Coming up with a stable formulation of ASAQ Winthrop® was challenging. An innovative bi-layer formulation was developed by Ellipse Pharmaceuticals (Bordeaux) and, when packaged in a double aluminium foil blister pack, resulted in a product with a three-year shelf life. This product was specifically adapted to patients’ needs, with the reduction of the number of tablets from six to one or two tablets once a day, for three days – in packs with pictograms, logos, and colours for ease of use by patients unable to read. The highest standards of quality were met. The product was readily dissolved in water and therefore easy to administer to infants and young children. Sanofi, the industrial partner, already involved in early development stages of co-blister development, committed to making the product available ‘at cost plus’ a small margin, at 1 USD for adults and 0.5 USD for children, and shouldered the required R&D efforts to register, manufacture in Africa, and distribute the product. Since being first registered in 2007 in Morocco, ASAQ Winthrop® is now available in 30 African countries, India, Ecuador, and Colombia, with its WHO pre-qualified status (acquired in 2008) making it eligible for tender by procurement agencies. A post-registration international programme to monitor ASAQ efficacy and safety in the field was launched with Sanofi and MMV and was the first Risk Management Programme of its kind to be submitted to the WHO. The non-exclusivity agreement with Sanofi allowed for increased access and subsequent technology transfer to Zenufa in Tanzania, which will ensure a second source of the ASAQ Winthrop® product in the future. To date, more than 400 million treatments of ASAQ FDC have been distributed worldwide, including products developed by generic companies.
Similarly, the ASMQ FDC was developed by the FACT consortium with Farmanguinhos/Fiocruz in Brazil and launched in Brazil in 2008. It was subsequently also manufactured by Cipla Ltd in India as the result of a successful South-South technology transfer agreement. It is now additionally registered in India, Malaysia, Myanmar, Tanzania, Vietnam, Niger, Burkina Faso, Thailand, Cambodia, Niger, Tanzania, and Burkina Faso; the re-introduction of ASMQ as first-line treatment in 5 provinces of Cambodia in 2014, despite concerns of increasing resistance to ACTs in the region, reflects the role ASMQ could play in the Great Mekong Region. The Cipla product was pre-qualified by the WHO in 2012. As a highly effective treatment in Africa, ASMQ FDC may also have a role to play in a multi first-line therapy approach, as currently practised in Ghana. The introduction of such policies, based on using several ACTs with comparable efficacy as first-line treatments, not only provides flexibility in treatment choice, but more importantly is aimed at reducing the drug pressure on the parasitic pool that can lead to drug resistance. To date, over 800,000 treatments of ASMQ FDC have been distributed.
Both products are included on the WHO’s Essential Medicines List.
The power of partnership and dedication
These two projects demonstrate the ability of new, innovative partnerships between public and private actors, with a strong commitment from endemic countries to develop, deliver, and disseminate new high quality, affordable treatments within a short time frame. The dedication and commitment of the members of the FACT consortium, chaired throughout by Professor Nick White, has been invaluable, and its success is notably due to the enormous contribution of Jean-René Kiechel, PhD, who has led the DNDi malaria portfolio since its inception.
‘ASAQ and ASMQ fixed-dose antimalarials were among the first challenges in developing new treatments that we took on at the outset of DNDi and these two projects have now reached fruition’, said Dr Bernard Pécoul, Executive Director of DNDi. ‘We have learned and gained incredible experience in terms of the development process, the innovative partnerships formed, and pathways forged, as well as the rapid implementation of the treatments to reach patients. These projects have proved how essential a nimble partnership model is to success, and how crucial the engagement and dedication of numerous public and private partners, and individuals, are to reaching a common goal.’
Handover of DNDi malaria programme to Medicines for Malaria Venture (MMV)
MMV and DNDi have agreed that the ASAQ and ASMQ products developed by DNDi and its partners will now be managed by the MMV Access and Product Management team to help maximize their impact for the patients who most need them.
‘The goal is to ensure these medicines reach as many vulnerable people as possible and save lives’, said Dr David Reddy, CEO of MMV.
Since being founded 15 years ago, MMV, working with its partners, has successfully built the largest ever pipeline of antimalarials, including five new therapies currently reaching patients in malaria-endemic countries.