Antimalarial Activity of Artefenomel Against Asexual Parasites and Transmissible Gametocytes During Experimental Blood-Stage Plasmodium vivax Infection

Background Interventions that effectively target Plasmodium vivax are critical for the future control and elimination of malaria. We conducted a P. vivax volunteer infection study to characterize the antimalarial activity of artefenomel, a new drug candidate. Methods Eight healthy, malaria-naive participants were intravenously inoculated with blood-stage P. vivax and subsequently received a single oral 200-mg dose of artefenomel. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma artefenomel concentration. Mosquito feeding assays were conducted before artefenomel dosing to investigate parasite transmissibility. Results Initial parasite clearance occurred in all participants after artefenomel administration (log(10) parasite reduction ratio over 48 hours, 1.67; parasite clearance half-life, 8.67 hours). Recrudescence occurred in 7 participants 11-14 days after dosing. A minimum inhibitory concentration of 0.62 ng/mL and minimum parasiticidal concentration that achieves 90% of maximum effect of 0.83 ng/mL were estimated, and a single 300-mg dose was predicted to clear 10(9) parasites per milliliter with 95% certainty. Gametocytemia developed in all participants and was cleared 4-8 days after dosing. At peak gametocytemia, 75% of participants were infectious to mosquitoes. Conclusions The in vivo antimalarial activity of artefenomel supports its further clinical development as a treatment for P. vivax malaria.

Automated summary

This study evaluated the antimalarial activity of artefenomel, a new drug candidate, against P. vivax malaria. The results showed that artefenomel effectively cleared parasites after oral administration, but recrudescence occurred in some participants. The minimum inhibitory concentration and parasiticidal concentration were estimated, and a single 300-mg dose showed a high efficacy in clearing parasites. Gametocytemia was observed in all participants and cleared after dosing. Overall, the findings support further clinical development of artefenomel as a treatment for P. vivax malaria.