Passing the ball: DNDi transfers malaria therapies to MMV

The Drugs for Neglected Disease initiative (DNDi) and the Medicines for Malaria Venture (MMV)—nonprofit product development partnerships (PDPs) and members of the Global Health Technologies Coalition—have teamed up to ensure two treatments for malaria continue to reach the patients who need them most. The treatments—two fixed-dose artemisinin combination therapies (ACTs) known as ASAQ and ASMQ—were developed by DNDi and partners and launched in 2007 and 2008, respectively; going forward, MMV will work with those partners to ensure these drugs remain available and accessible in countries where they are most needed.

To commemorate the handover, DNDi CEO Dr. Bernard Pécoul passed the ball—a literal rugby ball—to MMV CEO Dr. David Reddy during a side event at the 68th World Health Assembly in Geneva, Switzerland.

We’re joined by Jean-René Kiechel, PhD, Senior Pharma Advisor & Product Manager of DNDi and George Jagoe, Executive Vice President of Access & Product Management at MMV to learn more about this handover and the existing and potential impact of these medicines.

Q: What impact could ASAQ and ASMQ have in the fight against malaria?

The FACT (Fixed-Dose Artesunate Combination Therapy) consortium was formed in 2002 to develop combinations of artesunate (AS) with amodiaquine (AQ) or mefloquine (MQ). These treatments were recommended by the World Health Organization (WHO) in response to increasing chloroquine resistance, but were not available in easy-to-use fixed-dose combinations (FDCs). The FACT consortium was transferred to DNDi when the organization was created in 2003. It led to the creation of two FDCs:

ASAQ: In 2007, ASAQ Winthrop® became the first treatment to be launched by DNDi. It was developed by a number of partners across almost the full development range, from formulation work to post-registration studies. There were significant challenges to overcome, including developing a stable bilayer formulation of the two drugs, together with the aluminum blister packaging designed to withstand the rigors of a tropical environment. Manufacturing and distribution of this stable formulation were undertaken by Sanofi, who were already providing co-blistered Coarsucam™ to Africa at the time, and who committed to making the generic ASAQ Winthrop® available at less than US$1 per adult treatment for the public market.

ASAQ’s low price and prequalified status, which allows purchase by procurement agencies, led to price decreases not only of ASAQ but also for other ACTs. Lower drug costs led to increased patient access to high quality treatments. To date, more than 400 million treatments of ASAQ have been distributed worldwide, including products developed by generic companies.

ASMQ: Launched in 2008, ASMQ was developed in collaboration with Farmanguinhos/Fiocruz, a Brazilian public pharmaceutical company. A South-South technology transfer agreement to Cipla Ltd in India ensured a second supplier of the treatment, principally for the Asian market but also for Africa.

Recent results from a multi-center trial carried out in Africa showed ASMQ is as efficacious as artemether-lumefantrine—Africa’s most widely adopted treatment—in children under 5 years of age, and is well tolerated. ASMQ also demonstrated high cure rates and good efficacy in a number of studies in Asia and Latin America, including a large intervention study in Brazil with more than 23,000 patients. In a study comparing five ACTs in Myanmar, ASMQ FDC showed the highest cure rates, the lowest rates of gametocyte carriage (which are believed to affect the transmissibility of malaria), and provided the best post-treatment suppression of malaria.

By the end of 2014, 832,000 ASMQ treatments had been distributed.

Q: DNDi and MMV are both product development partnerships. What value do you see in collaborating with one another and what inspired this handover?

In May 2015, in order to ensure the best future implementation of these two treatments, DNDi handed over its malaria program to MMV. MMV is a long-term partner of DNDi, and is managing the largest portfolio to date of antimalarial drugs—from all phases of drug discovery, development, and delivery.

Collaboration is at the heart of the PDP model. The PDP is a form of public-private partnership whereby a varied collection of partners collaborate in a flexible, 'virtual' model. This includes biotech, pharma (large and start-up), nongovernmental organizations (NGOs), academia, and private and public sponsors who operate in the disease-endemic countries or globally. A key requirement for these participants from very different backgrounds is agreement on a specific common goal and specific objectives that address the disease in question while at the same time being guided by WHO priorities, the needs of country control programs, and ad hoc experts.

The direct, open dialogue between partners who normally do not work together (and may even compete) promotes creativity and out of the box thinking. It fosters the innovation and creativity required to overcome the many challenges that arise in product development.

PDPs such as MMV and DNDi have helped to address major market failings in malaria drug development. By enhancing the focus of drug research partners and by mobilizing donor funding for this critical work, both organizations have shown that this model of research and development can make a huge impact on the lives of patients suffering from diseases that have historically been neglected by most pharma companies. Thanks to the collaborative approach that MMV and DNDi have taken in orchestrating the hand-off of ASMQ and ASAQ, both organizations have been able to refine their focus areas for the future.

Q: What role have diverse geographic and cross-sector partnerships had in the development and introduction of ASAQ and ASMQ?

Both ASAQ and ASMQ demonstrate the ability of innovative private-public partnerships, with a strong commitment from endemic countries, to develop, deliver, and disseminate new high-quality, affordable treatments within a short time frame.

ASAQ Winthrop® is a case in point: the partnership that led to the development and registration of ASAQ Winthrop® had to ensure the new drug's successful launch and adoption by endemic countries. First among the many partners needed at this crucial stage are endemic countries' national malaria control programs. Sanofi and DNDi engaged in collaborations with a number of other partners to facilitate the implementation and availability of ASAQ Winthrop®, including experts, WHO, research institutes, funding agencies, and other NGOs. For example, DNDi coordinated a clinical study with the Indian Council of Medical Research to facilitate the adoption of a new anti-malarial policy in India. This study allowed for the registration of ASAQ Winthrop® in India.

DNDi also convened an independent panel of experts, the FACT Implementation Advisory Group, to provide independent advice and critical guidance about issues related to implementation and rational use of ASAQ Winthrop®, ensuring equitable access.

Another example of the power of partnerships is the DNDi partnership with Sanofi, MMV, and national malaria control programs in Africa. The aim is to collect high-quality data on ASAQ effectiveness and safety, as part of a Risk Management Plan. This is the first of its kind to be submitted to the WHO, and the first to be set up entirely in Africa. It involved some 15,000 patients in one of the studies carried out in Côte d’Ivoire, collecting data on the drug’s safety and effectiveness in real-life conditions. Results are expected to be published by the end of 2015.

Q: What are the next steps in ensuring these products are available to the people who need them most?

To support uptake of new medicines like ASMQ and ASAQ, several hurdles must be overcome. These include:

• Inclusion of the medicines by WHO in standard treatment guidelines.
• Adoption by national disease control programs.
• National registration by drug regulatory authorities.
• Education and training on the use of the medicines.
• Dissemination of new safety and efficacy evidence post-launch.
• Mobilization of requisite funding for procurement and introduction.

As a widely used ACT, ASAQ has met many of these challenges and will continue to play an important role in malaria treatment for many years to come. With new evidence emerging about ASMQ’s efficacy and tolerability, MMV and partners will target broader registration and use of this drug in Latin America, Southeast Asia (where its role in containing drug-resistant strains of malaria is critical), and in Africa, where it has had little use to-date.