MMV’s mission is to treat and protect people from malaria today, and develop next-generation medicines for tomorrow that will contribute to the eradication of the disease. In line with global frameworks from the World Health Organization and the United Nations, MMV will seek to maximize the impact of medicines for malaria control and elimination over its next business-planning period (2017–2021) by focusing on three strategic areas of activity:
- Facilitating equitable access to quality antimalarials to maximize the use and health impact of existing products (near-term).
- Developing better medicines for case management, including patient-adapted new combinations to overcome drug resistance, to facilitate deployment of shorter treatment courses and to protect vulnerable populations like children and pregnant women (medium-term).
- Bringing forward new tools for resistance and elimination to help countries reduce transmission and ultimately become malaria free (long-term).
To facilitate access (1), MMV works with partners and key global and country-level stakeholders. This effort includes gathering data on the tolerability of new medicines specifically in vulnerable populations and in ‘real-world’ settings to support their registration and adoption into relevant policies and guidelines; securing sustainable supply by diversifying the manufacturing base of existing medicines; and scaling-up use in-country.
For MMV’s research and development work (2 & 3), given the 12 to 15- year timeline from discovery to launch of a new medicine, it is important to define, at the very outset, the characteristics of the medicines needed. This is described by two Target Product Profiles (TPPs).
The first TPP, a Single Encounter Radical Cure and Prophylaxis (SERCaP) as proposed by the malERA Consultative Group on Drugs in 2011,1 remains a priority. Such a single-dose treatment would be effective against resistant strains of malaria, cure clinical malaria, stop transmission and prevent relapses. It would also simplify case management and improve compliance.
The second TPP is for chemoprotection drugs for non-infected people entering an area of high-malaria endemicity. The goal is to develop a Single Exposure Chemoprotection (SEC). Compounds used for this indication would need to have distinct mechanisms of action compared to those used for treatment.
Ideally, both groups of medicines would be universally well-tolerated, including in vulnerable populations and those with co-infection, and thus be suitable for Mass Drug Administration (MDA) – an approach that could help accelerate the trajectory to elimination and eradication by depleting the human parasite reservoir on a regional basis.2 Additional pharmacovigilance studies of medicines post launch will be required to confirm this level of safety.
Although 3 days is the minimum acceptable regimen, we continue to work towards the development of a single exposure medicine. However, this goal places an extraordinary demand on a molecule in terms of the required pharmacokinetics, potency, absolute dose, safety, tolerability and formulation. Consequently, we recognize that a trade-off might have to be navigated between single- and multiple-dose therapies, particularly when the latter show activity against known resistant strains and isolates.
The development of SERCaP or SEC will require the combination of at least two molecules. Thus, we have defined five Target Candidate Profiles, corresponding to different clinical attributes needed for the TPPs, and built a strong portfolio of molecules with diverse or competing mechanisms to combat resistance. As we hunt for molecules for SERCaP and our understanding of their characteristics grows, some of these molecules could be reprioritized and developed for the treatment of severe malaria; chemoprevention for vulnerable groups living in endemic regions; or as endectocides, which reduce survival of the mosquito vector and thereby malaria transmission.
MMV is currently working with 160 partners around the world to put this strategy into action. In 2016, our partner network was augmented by the addition of Janssen Pharmaceuticals, Zydus Cadila, India and S Kant Healthcare, India. Our partners are critical to our work to discover, develop and deliver antimalarials to treat and ultimately help eradicate malaria for good.
1. malERA Consultative Group on Drugs. “A research agenda for malaria eradication: drugs”. PLoS Med. 8(1):e1000402 (2011).
2. World Health Organization. Guidelines for the treatment of malaria. Third edition (2015).