White, Nicholas J, Pukrittayakamee, Sasithon, Phyo, Aung P, Rueangweerayut, Ronnatrai, Nosten, François, Jittmala, Podjanee, Jeeyapant , Atthanee, Jain, Jay Prakash, Lefevre, Gilbert, Li, Ruobing, Magnusson, Baldur, Diagana, Thierry Tidiane and Leong, Franz Joel Wen (2013) The novel spiroindolone KAE609 clears parasitemia rapidly in falciparum and vivax malaria. The novel spiroindolone KAE609 clears parasitemia rapidly.

Abstract

BACKGROUND
KAE609 (NITD609) is a novel synthetic antimalarial spiroindolone analogue with potent, dose-dependent antimalarial activity against asexual and sexual stages of Plasmodium falciparum in vitro. It is the first molecule with a novel mechanism of action to enter phase 2 studies for the treatment of malaria for 23 years.
METHODS
We conducted a phase 2 open-label study at three centers in Thailand to assess the antimalarial efficacy, safety, and tolerability of KAE609, 30 mg/day for 3 days, in two sequential cohorts of adult patients with uncomplicated Plasmodium vivax or P. falciparum malaria.
RESULTS
Overall, KAE609 was well tolerated. KAE609 cleared parasites very rapidly; the median parasite clearance time was 12 hours in both cohorts (interquartile range [IQR]: 8–16 hours and 10–16 hours in P. vivax and P. falciparum cohorts, respectively) and, after 48 hours, all patients were aparasitemic. The median parasite clearance half-life in falciparum malaria (N=11) was 0.9 hours (range: 0.68–1.64; IQR: 0.78–1.07) and in vivax malaria (N=10) was 0.95 hours (range: 0.68–2.01; IQR: 0.85–1.14). These rates of parasite clearance are faster than those with other classes of antimalarial drug, including the artemisinin derivatives. All patients completed treatment and recovered uneventfully. KAE609 was eliminated relatively slowly (mean terminal elimination half-life 21 hours), supporting a once-daily oral dosing regimen.
CONCLUSIONS
KAE609, 30 mg daily for 3 days, was well tolerated and very rapidly effective in adult patients with uncomplicated P. vivax or P. falciparum malaria.

Item Type:	Article
Keywords:	KAE609, NITD609, malaria, Plasmodium falciparum, Plasmodium vivax
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/20306