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Table 1 Critical characteristics of four potential antimalarial drug candidates

From: Challenges to replace ACT as first-line drug

  KAE609 KAF156 OZ439 OZ277
Potential partner drug? Ferroquine Solid dispersion formulation-lumefantrine Piperaquine ferroquine Piperaquine
Drug half-life (h) 21 48–60 46–62 2–4
Efficacy PCt1/2 0.9 h PCt1/2 3.5 h PC1/2 = 4.4 (WT K13) PC1/2 = 5.5 (Mutant) Median PCt = 24 h same as coartem
PCR-corrected ACPR on day 42 was under 50% with single dose piperaquine PCR-corrected ACPR on day 42 was >98% in both groups
Transmission blocking Reduction in stage 5 gametocyte in vitro and inhibit oocyst development in standard membrane feeding assay Reduction in stage 5 gametocyte in vitro and inhibit oocyst development in standard membrane feeding assay 7 patients with pre-treatment and 10 patients with post-treatment Pf gametocytes; one had up to day-6 Day 7 and Day 14 carriage higher than coartem [23]
Adverse event Raised transaminase (3/21 patients) Raised transaminase (30% of patients) 12/82 patients increased CPK 6.9% (49) got QTcF > 500 ms compared to 1.7% (6) in coartem
7/82 patients increased transaminases
2/82 patients QTcF > 450 ms. 18/82 patients with prolongation of QTcF > 30 ms from baseline
Resistance SNP at PfATP4 gene can be selected in vitro after 4-months exposure to incremental increasing conc. of KAE SNP at PfCARL gene can be selected in vitro after 4-months exposure to incremental increasing conc. of KAF Slower PCt1/2 in K-13 mutation even though in vitro RSA suggested no difference Not tested
MIC 0.1 ng/ml   4.1 ng/ml [17]  
  1. Conc., concentration; K13, PF3D7_1343700 kelch propeller domain; MIC, minimal inhibitory concentration; ng, nanogram; ml, millilitre; ms, millisecond; PCR, polymerase chain reaction; PCt, parasite clearance time; Pf, Plasmodium falciparum; PHEIC, Public Health Emergency of International Concern; RSA, ring-stage survival assay; SNP, single nucleotide polymorphism; WT, wild type