A message from MMV's CEO, David Reddy
Despite another year of uncertainty and challenges bought about by the ongoing COVID-19 pandemic, MMV and partners have remained firm in their commitment to continue the discovery, development and delivery of new antimalarials. The team made significant progress in addressing a range of unmet patient needs – see ‘2021 in Review’ below. Our approach has been to work even closer with partners to help address immediate challenges to malaria control presented by the pandemic, while simultaneously pushing forward on the projects that will serve the fight against malaria in the years to come.
Like many in the malaria community, we were shaken by news from the World Malaria Report 2021 of a greater loss of life from malaria than previously thought. An estimated 627,000 people lost their lives to malaria in 2020. Of these deaths, 602,000 (96%) were in Africa. It is noteworthy that during the same year there were 541,000 deaths from COVID-19 in Europe and 508,000 in North America. These statistics underscore the heart-breaking scale of malaria mortality – particularly when 80% of those dying from the disease are children under the age of 5 years.
MMV has had considerable impact along the entire malaria research value chain over the last decade: A robust pipeline of 65 MMV-supported projects; enduring partnerships with 158 leading clinical centres across the world, including in 31 malaria-endemic countries; over 100 clinical trials with research partners in Africa over the last 5 years; and most importantly, around 3 million precious lives saved thanks to 13 quality medicines brought forward by MMV and partners.
We continue to build on these successes, redoubling our focus on bending the curve towards eradication and away from malaria resurgence with a strategy that recognizes short- and long-term malaria needs.
Once again, the WMR has stated the urgent need for increased support of research into new tools, especially as the threat of artemisinin resistance in Africa has become all too real. We are proud that MMV has shown significant progress in advancing promising next-generation antimalarial compounds to counter resistance. Progress in other areas include MMV’s work with partners to help over 33 million children in 13 Sahelian countries receive seasonal malaria chemoprevention (SMC) – a proven, protective intervention. When combined with the WHO-endorsed RTS,S vaccine, SMC has demonstrated an even greater protective impact in children, and some countries are considering its joint implementation.
We are working to tackle gender inequity in health by prioritizing the unmet needs of pregnant women and their babies, who are at high risk from malaria, yet have little in terms of targeted treatment. We have not lost sight of the unmet needs of millions who suffer from relapsing P. vivax malaria, working with partner GSK to ensure access to tafenoquine, a single-dose liver treatment for relapse prevention. In parallel, we are deepening our role in the supply chain security space, intensifying our focus on bringing the manufacture of selected malaria medicines closer to where patients need them.
MMV possesses the assets, partnership network and scientific and technical capacity needed to help turn the tide of malaria by 2030. At the same time, MMV is also leveraging these capabilities to contribute to the ongoing effort against COVID-19. However, we cannot get closer to the end of these epidemics without the means. Funding remains a lifeline for all sections of the malaria community, including research and development. Sustained and increased funding and stronger multi-sectoral partnerships are primary drivers to spur and speed progress; and we applaud the WMR’s call for donors to treble funding to achieve the 2030 goals.
Finally, I would like to thank our outgoing Chairman, Per Wold-Olsen for his superb leadership and support during his tenure as Chairman of MMV’s Board of Directors, and Vice-Chair before that. I would also like to thank Dennis Schmatz and Win Gutteridge, who have also reached the end of their terms of Board office. Both Dennis and Win also served, at various times, as Chairmen of MMV’s Expert Scientific Advisory Committee (ESAC), and Dennis as ad-interim MMV CEO prior to my arrival. At the same time, I am delighted to welcome Alan Court as our new Chairman.
As we bid goodbye to yet another difficult year, I would like to thank all our partners and donors – who fully join us in their commitment to malaria eradication. Rest assured that our work will not stop until we reach our goal – a malaria free world.
I wish you a restful end of year and a healthy 2022.
2021 in review
Global Health Security and malaria
New combinations in the pipeline to counter resistance
- The threat of artemisinin resistance emerging in Africa has become all too real. In response, MMV and Novartis have advanced ganaplacide-lumefantrine, the front-runner non-artemisinin combination therapy. In September this year, we were delighted to report positive results of the Phase II study of the combination. Depending on the results of ongoing studies, this exciting combination could soon progress to Phase III clinical trials.
- We have also been working with partners to test other combinations including ZY19489-ferroquine, and M5717-pyronaridine, and expect to assess several others from 2022 onwards (M5717-ZY19489; ZY19489-Pyronaridine).
Relapsing P. vivax malaria – no longer neglected
- Since the approval of tafenoquine (TQ) in 2018 in the US and Australia as a single-dose treatment for relapsing malaria, MMV and partner GSK have been working to ensure access in P. vivax endemic countries.
- Remaining areas of focus include implementing TQ alongside a quantitative G6PD test to minimize the risk that G6PD-deficient patients might receive the medicine, and identifying alternative blood-stage treatment strategies in areas of CQ resistance.
- Meanwhile, Brazil, Thailand and Peru have granted marketing authorization for TQ in adults receiving CQ for blood-stage treatment and patients with P. vivax malaria in Manaus and Porto Velho in Brazil have begun receiving a new treatment protocol as part of an innovative programme led by the Ministry of Health, representing the first-ever, large-scale real-world, use of TQ and G6PD testing.
- Seven other countries are reviewing the TQ dossier for regulatory approval (Colombia, Ethiopia, India, Myanmar, Philippines, Pakistan and Vietnam) and GSK has filed a paediatric label extension in Australia, with approval expected in early 2022. This includes a new 50 mg dispersible tablet specifically for young children. With funding provided by Unitaid, MMV is also supporting the development of a quality-assured, child-friendly formulation of primaquine.
- Feasibility studies looking at the best way to use different P. vivax relapse treatments and diagnostics at different levels of the healthcare system in malaria endemic countries, including Ethiopia, India, Indonesia, Papua New Guinea, Peru and Thailand are being designed by MMV, PATH, Menzies, Burnet Institute and partners as part of the Partnership for Vivax Elimination (PAVE) with funding from Unitaid and others.
Deepening our role in the supply chain security space
- In 2020, we accepted to co-lead a multi-partner workstream focused on monitoring and mitigating risks to global supply chain security during the pandemic – tracking the manufacture and delivery of malaria medicines and other commodities.
- In 2021, we intensified our focus on bringing the manufacture of selected malaria medicines closer to where most patients need them by providing technical support to three pharmaceutical companies (Emzor and Swipha in Nigeria; UCL in Kenya). UCL’s dossier for the manufacture of sulfadoxine-pyrimethamine to protect pregnant women from malaria is currently being reviewed by WHO Prequalification with feedback expected shortly.
- In addition, to counter manufacturing disruptions that destabilize medicinal supply chain security, MMV has been working since 2018 with S Kant Healthcare to develop a child-friendly, affordable formulation of SPAQ for Seasonal Malaria Chemoprevention (SMC) called Supyra®. The drug was granted WHO prequalification in April 2021.
In support of COVID-19
Compound screening: With partners worldwide, MMV’s support for screening of compounds against SARS-CoV-2 resulted in three publications and included facilitated collaboration between partners from Brazil, Scotland and South Africa among others.
Modelling and simulation: MMV provides ongoing support to several other COVID-19 related research initiatives, including modelling and simulation platforms to predict: (i) potential drug-drug interactions between Ivermectin and ASAQ (in the DNDi-led ANTICOV study); (ii) drug concentrations in human lung epithelium for two antimalarials, amodiaquine and its active metabolite desethylamodiaquine; and pyronaridine.
Clinical development: MMV is supporting the progression into clinical development of ASAQ (in the ANTICOV and MMV-sponsored ReACT studies); and Pyramax® (pyronaridine-artesunate) (in the ReACT study). ReACT is now complete, and the data being analyzed, with a read-out expected in early 2022.
MMV’s partner, Shin Poong, completed Phase IIb trials of Pyramax to treat mild to moderate COVID-19 patients in Korea earlier this year. MMV assembled an expert virology advisory board and provided technical advice to Shin Poong. On the back of the Phase IIb findings Shin Poong initiated a Phase III study enrolling their first patient in Korea in October.
The unqualified success of Seasonal Malaria Chemoprevention (SMC)
For 6 years, MMV has played a vital role in the implementation of WHO-recommended SMC, sulfadoxine-pyrimethamine plus amodiaquine (SPAQ), ensuring the scale-up of manufacturing to provide over 100 million SPAQ courses annually and coordinating regional collaboration amongst the 13 Sahelian countries now routinely deploying the intervention.
- This cost-effective tool has reduced the burden on national health systems, promoted good health practices, helped regulatory authorities improve pharmacovigilance and has become a benchmark of how “treatments should progress from research to practice”. In 2020 alone, despite COVID-19 disruptions, MMV and partners helped over 33 million children receive SMC in the 13 countries, 12 million more than the previous year.
- With MMV’s support, S Kant Healthcare has received WHO prequalification for its child-friendly SMC therapy Supyra (noted above). This makes S Kant the second manufacturer of quality-assured, child-friendly SPAQ, providing both increased supply and greater security of supply for this important SMC therapy.
- MMV is now leading two new SMC initiatives: SMC Impact to provide evidence to expand SMC to children aged 5-10 years and increase the number of visits by community healthcare workers in areas where the rainy season lasts longer; and OPT-SMC to enhance the capacity of National Malaria Control Programmes to conduct implementation research, which will support with health systems’ strengthening.
- The success of MMV’s SMC campaigns has demonstrated the utility of drug-mediated disease prevention in malaria. When combined with the WHO-endorsed RTS,S vaccine, SMC has also demonstrated a greater protective impact in children, and some countries are considering its joint implementation.
Tackling gender inequity in health
It is well known that pregnant women are at high-risk from malaria, yet they have little in terms of targeted treatment. The unmet needs of pregnant women and their babies are top priority for MMV.
- Through the Malaria in Mothers and Babies (MiMBa) initiative, MMV has been accelerating innovative drug development and deployment strategies to identify and deliver new medicines adapted to the needs of pregnant and lactating women.
- The MiMBa strategy aims to raise the standard of care for pregnant women and their newborns affected by malaria. Its activities include ensuring drug supplies for children and pregnant women, generating data on the impact of existing compounds in pregnant women, lactating women and neonates and developing new antimalarial medicines deemed low risk to the developing foetus.
- Furthermore, MMV and Liverpool School of Tropical Medicine (LSTM) have collaborated to establish pregnancy registries in malaria-endemic countries across sub-Saharan Africa that prioritize data collection to increase the number of appropriate antimalarial options for women through pregnancy. The registries are helping to fill the data gap on the use of antimalarial medicines during pregnancy.
Largest real-life study of Pyramax
- In response to the European Medicines Agency (EMA) request for a large study to provide supplementary assurance regarding real-life safety, in June 2021 MMV and Shin Poong Pharmaceutical Co. Ltd., published the largest real-life study of Pyramax® (pyronaridine-artesunate) for the treatment of uncomplicated malaria to date, with over 8,500 malaria episodes across five African countries: Gabon, Côte d’Ivoire, Cameroon, Congo Brazzaville, and DRC.
- The study conducted in partnership with the Central Africa Network on Tuberculosis, HIV/AIDS and Malaria (CANTAM) and other partners, reported high effectiveness, safety and tolerability under conditions similar to everyday clinical practice, supporting further uptake of the antimalarial in Africa.
- The study population included patients with acute hepatitis, as well as those with HIV, malnourished patients, children under 1 year of age and women who were unknowingly pregnant.
Need for new tools (pioneering developments to accelerate R&D)
A predictive tool for early assessment of resistance
With the rise and spread of P. falciparum resistance to existing therapies, researchers are urgently seeking to progress new compounds with new mechanisms of action and a high barrier to resistance.
- MMV devised a predictive tool to assess resistance to antimalarial compounds and guide their development. In May, Trends in Parasitology published MMV’s new strategy of resistance identification focusing on the drug discovery phase, which will allow early decisions to stop or deprioritize a compound/series if a significant risk of drug resistance is identified.
- This new strategy also includes a tool to assess the comprehensive resistance risk for a candidate drug early in the preclinical phase, even before it progresses into clinical trials. The aim is to inform investment decisions and, for early-stage testing, to improve the quality of compounds over time from a resistance perspective.
A new tool to accelerate candidate selection
- In December, MMV launched a free, innovative drug research tool, MMVSola, that aims to accelerate the selection of the best candidate drugs.
- MMVSola predicts (i) clinical pharmacokinetics (in malaria as well as other diseases) and (ii) the dose required to clear all malaria parasites from an adult patient weighing 70 kg. It can be used to make clinical predictions as early as the discovery phase, saving crucial time and resources.
- The greater the amount of data and the more advanced the compound, the greater the power of MMVSola in helping to discover and select the best possible candidates, and subsequently design better and more informative clinical trials.