PAMAfrica, a global MMV-led research consortium, is developing treatments for babies under 5kg, severe malaria and drug-resistant uncomplicated malaria.
The World Health Organization (WHO) reported an estimated 249 million malaria cases and 608’000 malaria-related deaths across 85 countries in 2022, with Africa bearing a disproportionate share of the burden, accounting for 94% of all cases and 95% of deaths globally. Children, infants, and pregnant women are most at risk of severe infection, with children under five years old accounting for 78% of all malaria deaths in Africa in 2022. Malaria is a vector-borne disease, which means it is spread by mosquito bites. The most common symptoms are fever, headache, and chills, but severe symptoms can include extreme fatigue, difficult breathing and multiple convulsions.
With early diagnosis and adequate treatment, medicines can reduce the impact of malaria, prevent death, and help drive progress towards malaria elimination and eradication. However, many challenges remain in the fight against the disease: medicines are not accessible to everyone and vulnerable groups like infants and women of child-bearing age lack adequate medicines tailored to their needs, due in part to their exclusion in clinical trials. With partial resistance to artemisinin derivatives, the mainstays of malaria treatment, observed in South-East Asia and Africa, researchers need to prepare the next generation of medicines to kill the parasite. This is where Medicines for Malaria Venture (MMV) comes in: the Geneva-based not-for-profit organisation works with around 150 global partners to discover, develop and deliver new effective and affordable antimalarial drugs. MMV is involved in the entire drug development pipeline, from early discovery to post-approval studies, and seeks to ensure that all populations benefit from its medicines. To date, their co-developed medicines have saved the lives of 15.4 million people.
In 2018, the European and Developing Countries Clinical Trials Partnership (EDCTP), named EDCTP2 for the 2014-2024 period, launched an innovative call for proposals asking for an “attractive research and development portfolio including one or more clinical trials relevant for target populations (pregnant women, infants and children).” This call aligned with MMV’s priorities. Inspired and convinced it could propose a winning portfolio, MMV contacted partners in Africa and Europe, as the actors in both regions share the goal of eradicating malaria, and could share knowledge, learning and understanding to achieve this goal. After bringing motivated partners together from pharmaceutical companies, European universities, and African research institutes, they formed the PAMAfrica consortium. Once aligned on the local realities endemic countries face and ensuring a collective approach to the planned clinical research, consortium partners were able to understand each other’s expectations, workflows and areas of expertise, effectively bringing everyone together as a high-functioning team to meet the EDCTP2 call programme criteria.
In October 2019, upon a positive independent evaluation, EDCTP2 awarded a €21.9 million grant to PAMAfrica, with consortium partners providing additional funding exceeding €22 million. This funding has allowed the consortium to support 11 African students aspiring to become the next generation of scientific leaders in Africa, and to develop clinical trials and train local researchers for three different work packages: i) identifying next-generation drugs for uncomplicated malaria, ii) developing the first-ever malaria treatment for newborns under 5kg, and iii) creating a new medicine to treat severe malaria.
Once PAMAfrica received the grant, consortium partners started working together on the three projects and the strengthening of capacity by recruiting students and developing training initiatives. MMV has served as PAMAfrica’s project coordinator and has contributed to the progress of the studies and the capacity-strengthening work. It took work to keep everyone motivated during the COVID-19 pandemic, as priorities shifted, meetings and travel were cancelled, and some partners were unable to work efficiently for health reasons and shutdowns. Even though MMV has considerable experience coordinating consortia and conducting clinical trials, this was the first time it led such a large and diverse portfolio in a single grant. However, the benefits of the collaboration continue to be worth the challenges faced: combining expertise will deliver better healthcare outcomes for target groups. The portfolio structure also brings other gains: another pharmaceutical company joined the consortium in 2022, developing a trial drug for one of the consortium’s three key clinical work packages, with one of their compounds showing promise in addressing drug-resistant strains of uncomplicated malaria.
With PAMAfrica set to conclude in 2024, consortium partners are still working together to achieve their original work package goals. To date, one work package has completed trials, and the team submitted the data for regulatory reviews of a new treatment for babies under 5kg in April 2024. Moreover, the work packages developing new treatments for uncomplicated and severe malaria are currently in phase 2 clinical trials, and on the capacity strengthening side, the final cohort of students is expected to graduate in 2025 and will be supported by a mentor to help their transition to post-doctoral studies.
MMV’s work does not stop at the PAMAfrica consortium; it is currently working on more than 30 projects and has launched an ambitious 2024-2030 strategy to continue curing patients, developing simplified therapies to boost patient compliance and stay ahead of drug resistance. Among the ongoing initiatives, MMV is involved in six additional consortia funded by EDCTP, which is now under the Horizon Europe programme for the 2022-2030 period under the name, Global Health EDCTP3 Joint Undertaking (GH EDCTP3 JU). Switzerland is currently not associated to Horizon Europe and is considered a ‘non-associated third country’ to the programme. This means Swiss entities like MMV cannot serve as project coordinator; it can be a consortium member but needs an external administrative coordinator in the European Union and a scientific coordinator in Africa, which MMV can support through the experience gained as the coordinator of PAMAfrica. Successful applications including Swiss entities will receive direct funding from the Swiss Secretariat for Education, Research and Innovation (SERI). MMV has to date received such funding as an associated partner in two new consortia: SEMA ReACT started in April 2023 and aims to generate data on treatment strategies that acknowledge and address the challenges faced by rural and vulnerable communities at risk of severe malaria infection; and SAFIRE, which will start implementing activities in June 2024 to study the safety of existing antimalarial treatments in the first trimester of pregnancy.
MMV’s commitment to helping people and saving lives allows it to develop projects with multiple co-funders. Its creativity, dedicated work, collaboration, and the transparency it promotes among consortium partners not only allows MMV to manage projects, but its innovative grant applications have also been reflected in some EDCTP3 grant criteria, such as the requirement for an African scientific coordinator.
Acknowledgments:
The PAMAfrica grant is part of the EDCTP2 Programme (grant number RIA2018SD-2306), supported by the European Union.
The SEMA ReACT grant is part of the Global Health EDCTP3 Joint Undertaking (grant number 101103191), supported by the European Union and the Swiss Secretariat for Education, Research and Innovation (SERI).
SAFIRE is part of the Global Health EDCTP3 Joint Undertaking (grant number 101145740), supported by the European Union, the Medical Research Council (UK) and the Swiss Secretariat for Education, Research and Innovation (SERI).