To help expedite the development of promising compounds, MMV is employing innovative new tools such as the Challenge Model and pharmacokinetic/pharmacodynamic (PK/PD) modelling. The Challenge Model enables us to test candidate medicines in volunteers inoculated with a small dose of malaria in a tightly controlled environment. Using PK/PD modelling, we are able to take raw data, such as that generated in the Challenge Model, to determine relationships between concentration and efficacy.
Taken together, these approaches have provided a granularity of data that was previously inaccessible, enabling us to understand quickly and affordably whether a compound will work in man and provide guidance on dose selection for subsequent studies. For example, with DSM265, we have been able to link safety, efficacy and dose together in 6 months to determine the optimal dose; versus the 2 years it would take using using conventional Phase I and Phase II trials.
1. What are the advantages of the Challenge Model?
First, it has the potential to reduce the size of Phase IIA clinical trials in malaria-endemic countries, which can be very difficult and time consuming to conduct. The second thing is that when you test an experimental antimalarial drug there is always a risk that if the drug doesn’t work people could come to harm. In the Challenge Model, patients have very low levels of parasites in their blood so we know that they won’t be harmed.
2. What has it been like to work with MMV on developing and using the Challenge Model?
There has been continuous communication and open sharing of information. MMV’s product development partnership model is particularly suited to collaborative relationships between academia, industry and pharma. MMV’s strength is its strong relationships and flexibility. Also, its viewpoint is different from that of a pharma partner, as they are not just looking at one drug but the overall need for malaria drug development and so their strategy supports that. It’s a more holistic approach. On the other hand, MMV obviously has budgetary constraints; a big drug company can throw large amounts of money and manpower behind one drug, while MMV is more constrained by the money that’s available.