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Dr Tim Wells

Dr Tim Wells is the Chief Scientific Officer of the Medicines for Malaria Venture (MMV), a leading product development partnership in antimalarial drug research. We asked him to highlight the important elements of the EDCTP-funded PAMAfrica project.


Within the PAMAfrica project, three different clinical studies (a single-dose cure, an injectable cure for severe malaria, and treatment for newborns) will be conducted. How are these connected?

Tim Wells (TW): A key challenge in malaria eradication is that resistance to current malaria drugs is always a threat. So, two of the studies are looking at ways of combating resistance. One strand is a treatment for uncomplicated malaria which could be simpler to deploy or usable when artemisinin combination therapies fail. The second is a new treatment for severe malaria, again potentially for when artesunate fails. The third strand is a little different and is about optimising current therapies for babies who are under 5 kg. In the future, this product may have the potential to be developed for use in underweight or malnourished children, currently an unmet need. These three workstreams are all key parts of the strategy to drive the elimination of malaria as a global public health risk. 

The clinical study aiming to find a single-dose cure uses a portfolio approach. In practice, how does this work?

TW: With the threat of drug resistance looming from South East Asia, we need new combinations of two or more molecules for malaria treatment. In our portfolio, there are five or six molecules which are contenders for such a combination. The portfolio approach enables us to pick the best molecules to put together, by allowing us to match profiles to provide optimal malaria efficacy and barrier to resistance, in discussion with all the partners. Ideally, we should take more than one combination into phase II studies, and let the clinical data help us decide which combinations to prioritize. This enables us to de-risk the portfolio by having more irons in the fire.

A second clinical study aims to find an injectable cure for severe malaria. What will be the clinical advantages of using cipargamin versus artesunate and/or artemether?

TW: Clinically, the impact of current artemisinin resistance today is that it slows down parasite killing by 2-3-fold. Cipargamin is the fastest killer of parasites seen from any MMV partner programme over the last 20 years. The molecule was originally discovered as part of a Novartis-led consortium funded by MMV and the Wellcome Trust. The phase II and III evaluation of this drug is funded by EDCTP. The rapid speed of kill of cipargamin may offer a real benefit for patients infected with artemisinin-resistant parasites, in rapidly reducing the overall parasitaemia and so stabilise these very ill patients. It gives us also another treatment in our armamentarium. We need to be ready to provide an alternative for patients who may not be able to access artesunate.

A third clinical trial will look for malaria treatment in newborns. How is the PAMAfrica approach different in targeting the needs of this vulnerable group?

TW: Currently, there is no approved malaria treatment for babies under 5 kg. Doctors still have to treat such patients, and so the best practice today is to give these children a full course of treatment approved for use in older children. In a previous study, our partner Novartis demonstrated that the ratio of the plasma concentrations for the two drugs changes in very small patients. So, this programme is looking at a regimen which has a lower artemether-lumefantrine ratio than that used in older children. What’s particularly exciting is that the lessons learned about drug development in this population can also be applied to any other therapeutic area for this same vulnerable population.

Dr Tim Wells

The project envisions a policy change in malaria treatment at both national and international levels. How will the consortium pursue this? 

TW: This is a really important question. Historically, MMV has worked with international experts, including those from National Malaria Control Programmes, to set the ‘target product profiles’ or TPPs. These TPPs are descriptions of the drugs that we aim to develop, both the minimum acceptable profile and the ideal profile. MMV has published these descriptions in the scientific literature over the last decade. Going forward we are working to align this process with the WHO Global Malaria Programme’s development of such TPPs. Continual discussion with all the public health stakeholders is an essential part of what we do here. Towards the end of PAMAfrica projects, key findings from the trials will be presented as policy briefs, for the attention of decision-makers at governmental and WHO level, including recommendations for the required policy changes. MMV will also work closely with WHO and local partners to ensure engagement with national malaria control programmes.

How do these three studies fit into the global MMV portfolio?

TW: The MMV portfolio has to balance the needs of the malaria elimination agenda. With PAMAfrica partners we have a boost to the ongoing work with new treatments – we already have molecules in phase II, and this would add another combination. It is a new paradigm where we hope to test more than one combination in parallel. For severe malaria, the pipeline is quite thin, and this approach with cipargamin not only tests a new drug but more importantly a new paradigm for clinical trials. Finally, for the treatment of babies under 5 kg, this will provide a medicine tailored to treat this population, as well as information on how to develop medicines for this under-served population. There are not many patients this young or small, but the lessons learned will help us better understand how to optimise medicines for use in this vulnerable patient group.

How is the research capacity and research site development embedded in the project? 

TW: Improving research capacity and clinical site development is a critical goal of the work of the PAMAfrica consortium. One of our work packages is to support clinical trial sites with aspects such as staff and infrastructure development. Managing clinical trials according to the highest quality standards is a critical success factor. The Manhiça Health Research Centre in Mozambique and MMV will co-lead the capacity-building activities.
Moreover, we see a real need to invest in and support the development of female researchers in Africa, both medical and non-medical. This will be a priority for us.

Dr Tim Wells

With the threat of drug resistance looming, we need to be ready to provide an alternative to patients.

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