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; <500Â mg/<100Â mg in infants. Simple oral formulation Injectable: subcutaneous or intra-muscular, once per month, with injection volumes <0.5Â ml for infants via a 25 gauge or smaller needle | Oral, once per month; <100Â mg, Injectable: subcutaneous or intramuscular once per 6Â 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 |