Antimicrobial resistance to antimalarials
Microbes naturally undergo mutations which, under the right conditions, can allow them to evolve resistance to the medicines used to treat them. This phenomenon, known as antimicrobial resistance (AMR)1, threatens the public health response to many diseases, including malaria. Resistance to antimalarials is a major health security risk in the Greater Mekong subregion of Southeast Asia2, and continued vigilance is needed in Africa where signs of resistance are appearing.3 The impact on lives lost could be devastating were resistance to antimalarial medicines to spread throughout Africa, where health systems are fragile and malaria morbidity and mortality are highest.
Research into new medicines is an invaluable insurance policy against the risk of drug resistance. MMV, with partners, has been successful in replenishing the drug pipeline for malaria, and its experience and strategies developed are relevant to sparking R&D innovation for diseases beyond malaria. The model at the base of MMV's work to bring forward new antimalarial medicines, including those capable of combatting resistance, is the Product Development Partnership (PDP) model.
Read on to find out more about the PDP model as applied by MMV, as well as MMV's strategy to tackle drug resistance.
The PDP model sparks innovation to contain resistance
The PDP model was brought into being in the late 1990's to address the dry pipeline of vaccines, diagnostics, and drugs for neglected diseases and diseases of poverty. The model uses public and philanthropic funds to engage the pharmaceutical industry and academic research institutions in undertaking R&D for diseases that they would normally be unable or unwilling to pursue independently, without additional incentives.
MMV reduces financial risk and adds value for money by gathering contributions from governments, pharmaceutical industries as well as philanthropic organizations. These joint investments — also known as syndicated investments — mean that a donor’s investment of one dollar creates 3.5 dollars of investment impact thanks to direct and in-kind support from MMV partners. Collaboration has been crucial, as this operating model allows partners to share not only risks, but also costs, ideas and efforts, driving the discovery of new medicines, leading to tangible results. And there are many: thanks to the innovative PDP model at the foundation of our work, MMV and partners have brought forward 12 antimalarial medicines since 1999, with an additional two brought into the portfolio post approval. These medicines are estimated to have saved 3 million lives. In addition, MMV's portfolio contains 11 new compounds, all of which are active against current resistant strains.
MMV's approach to tackling resistance to antimalarial medicines includes four pillars:
- Developing patient-friendly medicines, including children’s formulations and medicines with simpler dosing regimens (ideally, single-dose cures) which improve adherence to treatment and reduce the chances of resistance emerging;
- Developing and delivering only high-quality, WHO-prequalified medicines;
- Establishing discovery networks and assay platforms to accelerate the identification of molecules with activity against all known malaria parasite strains, as well as those resistant to currently available treatments. We also check to see how easily resistance can be generated in laboratory conditions and prioritize compounds that can eliminate parasites with a low risk of resistance developing.
- Supporting national malaria control programmes and other partners to deliver the right medicine to the right patient at the right time.
1. WHO definition of AMR: “Antimicrobial resistance happens when microorganisms (such as bacteria, fungi, viruses and parasites) change when they are exposed to antimicrobial drugs (such as antibiotics, antifungals, antivirals, antimalarials and anthelmintics)”.
2. WHO: Report on antimalarial drug efficacy, resistance and response: 10 years of surveillance (2010-2019)
3. Uwimana, A., Legrand, E., Stokes, B.H. et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med 26, 1602–1608 (2020).