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Table 4 TCP-1 profiles, molecules that clear asexual parasitemia

From: New developments in anti-malarial target candidate and product profiles

TCP-1 criteria at human proof of concept Minimum essential Ideal
Dosing regimen; adult/pediatric dose Oral, single dose (predicted) <1000 mg/<250 mg; oral, three doses <400 mg/<100 mg for areas of multidrug resistance Oral, single dose (predicted); <100 mg/25 mg
Rate of onset of action and clinical parasite reduction ratio from single dose Rapid clearance of parasites at least as fast as mefloquine (≤72 h from the highest burdens) and projected >106-fold reduction in parasites Immediate and rapid clearance of parasites at least as fast as artesunate; >Projected 1012-fold reduction in parasites
Susceptibility to loss of efficacy due to acquired resistance No fit and transmissible drug-resistant parasites identified; identification of combination partner with no cross resistance Very low (similar to chloroquine); no cross-resistance with asexual blood-stage combination partner. Resistance markers investigated
Relative clinical efficacy from patients in areas known to be resistant to current first line medications Clinical efficacy against all known resistance (3-day dosing) Clinical efficacy against all known resistance (single dose)
Drug- drug interactions No unsurmountable risks with potential anti-malarial partners No interactions with other anti-malarial, anti-retroviral or TB medicines
Safety Therapeutic ratio >tenfold between therapeutic exposure and NOAEL (no adverse effects level) in preclinical studies, and easily ‘monitorable’ adverse event or biomarker for human studies Therapeutic ratio >50-fold between therapeutic exposure and NOAEL in preclinical studies and easily ‘monitorable’ adverse event or biomarker for human studies
G6PD (glucose-6-phosphate dehydrogenase) deficiency status Measured—no enhanced hemolysis risk from testing in SCID mice engrafted with human blood from volunteers with reduced G6PD activity; clinical confirmation Measured —no enhanced hemolysis risk in subjects with reduced G6PD activity, with clinical confirmation
Formulation Simple and inexpensive to produce, not requiring proprietary methodology or kits; can readily be produced in endemic countries Simple and inexpensive to produce, not requiring proprietary methodology or kits; can readily be produced in endemic countries
Cost of active ingredient in final medicine Similar to current medication: ≤$0.5 for adults, $0.1 for infants under 2 years Similar to older medications: <$0.25 for adults, $0.05 for infants under 2 years
Estimated stability of final product under Zone IVb conditions (30 °C 75% humidity), in final packaging ≥24 months ≥3–5 years