A weapon to counter resistance

Dr Jörg Möhrle, Head of Translational Medicine, MMV

OZ439 is a fully synthetic peroxide on track to provide not only a single-dose cure for malaria, but also a potential alternative to currently used artemisinin derivatives. Its structure includes a peroxide bond, which is believed to be the artemisinins’ key weapon against malaria. Nonetheless, OZ439 is structurally very different from the artemisinins, making it likely to remain effective against artemisinin-resistant strains.

1. Why are we striving for a one-dose cure for malaria?

A one-dose cure could really change the malaria treatment landscape. Patients can be treated straightaway in front of the healthcare worker, assuring they always receive the complete dose. This is not just a matter of convenience; it will also help to prevent resistance developing against the medicine.

2. As the molecule has the same mechanism of action as artemisinin, how confident are you that it will be effective against artemisinin-resistant strains of malaria?

The only similarity between artemisinin derivatives and OZ439 is the endoperoxide bond. On this basis there is a reasonable chance that it will not be susceptible to the same resistance mechanisms occurring against artemisinin. But there still is a risk and so we can only be completely confident when we are able to test it in patients with artemisinin resistant malaria. We plan to begin a study in 2011 with the group from Mahidol University that initially identified the resistant strains in that same area.

3. What are the next steps for the development of OZ439 as a combination therapy and how soon could it be available?

In addition to the studies in artemisinin resistance patients, we have selected three potential partner drugs and begun the non-clinical work to evaluate which are compatible with OZ439. Once this has been completed we will test the combinations in healthy volunteers to evaluate their safety and tolerability. There is still some way to go, but if all goes to plan we could hope to see the medicine available by 2016/2017.