All shots on goal for a single-dose cure

Dr Fiona Macintyre, Associate Director, Translational Medicine, MMV

While ACTs are available and access to them is improving, MMV cannot rest on its laurels, but must continue to innovate and develop better medicines for uncomplicated malaria. There is a real need for medicines that are simpler and easier to take, such as a single-dose cure. Not only would such a medicine facilitate ‘directly observed therapy’, which would help to prevent the emergence of drug resistance, it would also reduce the cost of treatment.

2011 witnessed the continued progress of several potential antimalarial compounds through the pipeline. Results of the ongoing Phase IIa study of MMV’s synthetic endoperoxide OZ439 continue to show that the compound is not only potent, but also has the potential to become the breakthrough single-dose cure for Plasmodium vivax and Plasmodium falciparum infection. Furthermore, given the structural differences between OZ439 and the artemisinins, there is also hope that it will be efficacious against artemisinin-resistant strains of malaria. The challenge now is to find the right partner medicine and the right dose.

1. To protect against the development of drug resistance, the World Health Organization (WHO) recommends that every medicine should be combined with a partner drug. How will this drug be selected for OZ439?

At the moment we are considering four drugs as potential partners. The acid test to determine which we take forward will be the Phase IIb combination efficacy and safety clinical studies in malaria patients.

With four combinations to work on, before we get to that stage there is a tremendous amount of work to be done. We are currently conducting non-clinical and clinical safety studies on these drugs, both alone and in combination with OZ439 in an attempt to discriminate between them. It is really important that we conduct the right experiments at this point and carry them out thoroughly, to fully understand the pros and cons of each potential partner drug.

2. With such a complex development plan ahead, how will MMV ensure OZ439 is ready to treat patients as quickly as possible?

By conducting several projects in parallel, we increase the likelihood of success. It takes a finite amount of time to develop drug formulations for each combination and to conduct clinical studies. But if we conduct these studies for each partner, as far as possible in parallel, we can get to the point where we can make a fully informed decision on which combination to choose much faster than if we were to do them sequentially. This is why we are investing a great deal into this project now.

3. How will we know if OZ439 is fully efficacious against artemisinin-resistant strains of malaria?

We plan to test OZ439 in patients with potential artemisinin-resistant malaria. Testing in these patients is the only real way we can answer the question. The challenge, thankfully in many ways, has been to identify sufficient patients with whom to conduct the study.

We have partnered with Mahidol University scientists in Thailand to help identify further sites of artemisinin resistance. This will then allow us to decide the best place to conduct the study.