Artefenomel, a novel trioxolane, is a lead candidate for inclusion in a new antimalarial combination with a simpler dosing regimen, specifically formulated for children. Achieving an equivalent efficacy and safety profile in fewer doses than current 3-day ACT regimens is a major challenge. In partnership with Sanofi, MMV is aiming to overcome that challenge and is conducting a phase IIb trial of artefenomel in combination with ferroquine.
Artefenomel Project Leader at MMV, Dr Marc Adamy describes the potential of this compound, its current status and future plans.
1. What is exciting about artefenomel as a future antimalarial?
Usually antimalarial combinations are developed in adults and then later, potentially, in children. Artefenomel is the first antimalarial to be developed for children and adult populations in parallel, with the goal of accelerating access to the main target population, African children below 5 years of age. If we can develop a suitable artefenomel plus partner drug formulation and if it is confirmed efficacious against all P.falciparum infections (including those resistant to the major antimalarial drugs currently used in the field) it could be
a new ‘gold standard’, that is more convenient to take and therefore easier to adhere to. Although an ambitious goal, I am confident we will be able to improve on the current 3-day treatment regimens, with the aim of developing the combination as a single-dose cure.
2. In 2015, artefenomel was in phase IIb trials in combination with partner drugs, piperaquine (PQP) and ferroquine (FQ). What have we learnt so far and what are the next steps?
The artefenomel+PQP trial is now complete – 448 patients from eight countries participated in the trial which took 17 months from first patient dosed to topline results. This was the first-ever Single Exposure Radical Cure (SERC) programme we have conducted for malaria and provided a wealth of information. The upper dose of piperaquine tested was selected based on its safety profile; however, it did not reach a satisfactory efficacy level as part of the combination with artefenomel. Importantly, we were able to determine that a dose of 800 mg artefenomel was well tolerated.
We are now focusing our efforts on the development of the artefenomel+FQ combination and have transferred key methodological learnings from the artefenomel+PQP trial. These learnings relate to the selected drug doses that may be tested in young children, the importance of Directly Observed Treatment, and how to optimize patient recruitment. The artefenomel+FQ phase IIb trial started in July 2015 and we expect the results in 2018. As part of the clinical programme, we will also be looking at artefenomel’s activity in patients infected with emerging drugresistant strains of the parasite.
Meanwhile, we are investigating alternative partner drugs that, in combination with artefenomel, could meet the requirements of the SERC Target Product Profile.