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Table 6 TCP-4 profiles, as part of chemoprotection

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

TCP-4: general considerations Minimum essential Ideal
Dosing regimen; adult/pediatric dose Oral, once per week; <500 mg/<100 mg in infants. Simple oral formulation Injectable: subcutaneous or intra-muscular, once per month, with injection volumes <0.5 ml for infants via a 25 gauge or smaller needle Oral, once per month; <100 mg, Injectable: subcutaneous or intramuscular once per 6 months
Susceptibility to loss of efficacy due to acquired resistance No fit drug-resistant parasites identified in controlled human challenge model; no cross-resistance with partner drug in combination Very low; no cross-resistance with partner drug in combination; independent mechanism to those of treatments used in geographical area
Clinical protection from symptomatic infection >95% protective efficacy (positive parasitemia) >95% protective efficacy (positive parasitemia).
Bioavailability/food effect—human data >30%; no unmanageable food effect >50%/no significant food effect
Drug-drug interactions No unmanageable risks No interactions with other anti-malarial, anti-retroviral or TB medicines or oral contraception
Safety and tolerability Therapeutic ratio >tenfold between therapeutic exposure and NOAEL 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 deficiency status Therapeutic dose shows minimal change in hemoglobin concentration in subjects with reduced G6PD activity. New candidate drugs shows no enhanced hemolytic risk in preclinical model Measured—No enhanced risk in subjects with reduced G6PD activity
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 single treatment ≥$0.5 for adults, $0.1 for infants under 2 years per month for oral protection; injectable could be priced to vaccine levels <$0.25 for adults, $0.05 for infants under 2 years for oral treatment
Projected stability of final product under Zone IVb conditions (30 °C, 75% humidity) ≥3 years ≥5 years