(Interview took place in 2013)
In 2014, we saw the progress of several compounds able to meet the requirements of our TCPs with single-dose potential and therefore able to form the building blocks of a first generation Single Exposure Radical Cure and Prophylaxis (SERCaP).1
The most advanced compound, the aromatic trioxolane OZ439, is a molecule that MMV has taken from discovery right up to Phase IIB, where its efficacy in patients will now be determined. This will be the first time malaria patients will receive treatment with OZ439 in combination with a partner drug. Dr Marc Adamy explains the development plans to speed the progress of OZ439 to patients.
1. Given the emergence of artemisinin resistance and now treatment failures with ACT3 , next-generation antimalarials are urgently needed. What strategies have been employed to accelerate the development of OZ439?
In drug development, patient safety must be a top priority and so the process is highly regulated. With that in mind, the team is looking at innovative strategies to speed things up. For example, the typical route to drug development is to gather all the evidence in adults at least up to Phase II and then to start the paediatric development.
Given the huge burden of malaria in children, we will combine adults and children within the same Phase IIB programme. By adopting a staggered approach, starting first with adults, we will have safety results before moving to younger age groups and overall, will be able to expedite the process. Given the high level of unmet need presented by drug resistance and that OZ439 has demonstrated ex vivo efficacy against resistant parasites, the US Food and Drug Administration might consider it for fast track and/or breakthrough medicine designation. Either of these FDA statuses would help to bring an OZ439 combination therapy to patients in less time.
2. What are the next steps for the development of an OZ439 combination therapy?
The next step is to run two Phase IIB trials together, where we will test the OZ439/4-aminoquinoline combination. We will investigate the safety and efficacy of OZ/PQP and OZ/FQ in typical doseranging studies to select the optimal dose for Phase III. The trial should be complete around mid-2015. Phase III is scheduled to begin in 2016.
1. SERCaP: a medicine able to cure patients (targeting the blood stage) and eliminate the human reservoir of parasites (targeting the sexual stages). In addition, for radical cure of Plasmodium vivax malaria, the medicine would need to eliminate all blood-stage forms as well as hypnozoites in the liver. Finally, it would need to prevent reinfection of the treated individual for at least 1 month.