From: A discovery and development roadmap for new endectocidal transmission-blocking agents in malaria
TCP-6 criteria at human proof of concept | Minimum essential | Ideal |
---|---|---|
Dosing regimen | Oral, once monthly three daily doses of < 10 mg/kg | Oral, once monthly single dose < 2 mg/kg |
Action and clinical parasite reduction ratio from single dose | Efficacy of a Hazard ratio at least 4 is delivered upon mosquito feeding 28Â days post oral dose (for a use with SMC) | Rapid onset of action, within 12Â h. Efficacy equal or higher than a hazard ratio of 4 is delivered upon mosquito feeding 30Â days post oral dose |
Susceptibility to loss of efficacy due to acquired resistance in mosquitoes | No fit, fertile insecticide resistant insects in early resistance generation studies, no increase in cuticle thickening or selection for P450s which would reduce susceptibility to other insecticides | Idem |
Relative efficacy against mosquitoes highly resistant to current insecticides | Minimum activity on field An. arabiensis, An. gambiae and An. funestus via membrane feeding including strains with known insecticide resistance | Activity on all four major Anopheles species with malaria relevance in Africa |
Drug–drug interactions | No unsurmountable risks with potential anti-malarial partners, especially those under consideration for SMC | No interactions with other anti-malarial, anti-retroviral or tuberculosis medicines |
Safety | Safety margin > tenfold between therapeutic exposure and NOAEL in preclinical studies, and easily ‘monitorable’ adverse event or biomarker for human studies. | Safety margin > 50 fold and easily ‘monitorable’ adverse event. No reprotox safety signal in two animal species (‘Minimum’ for MDA, ‘Ideal’ for SMC). |
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. No food effect. |
Cost of active ingredient in final medicine | Similar to current anti-malarials: ≤ $0.5 for adults, $0.1 for infants under 2 years | Similar to older anti-malarials: < $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 | ≥ 2 years | ≥ 3–5 years |