Table 3 TPP-2 chemoprotection profiles
From: New developments in anti-malarial target candidate and product profiles
Parameter to be demonstrated for the combination in clinical evaluation | Minimum essential | Ideal single exposure chemoprotection |
|---|---|---|
Drug product | For elimination phases at least one of the two compounds also with TCP-4, co-formulated. The other should be a long-lasting blood schizonticide TCP-1 | For elimination phases both molecules should have TCP-4 activity, co-formulated |
Dosing regimen | Oral, once per week; injectable once per 3Â months | Oral once per month; injectable less frequently than once per 3Â months |
Rate of onset of action | For asexual blood-stage action—slow onset (>48 h) |  |
Clinical efficacy | ≥80% reduction in cumulative incidence of symptomatic malaria and non-inferior to Standard of Care | ≥95% reduction in cumulative incidence and non-inferior to Standard of Care |
Transmission blocking | No | Yes |
Bioavailability/food effect | Predicted or measured >30% for each molecule/less than threefold | Predicted or measured >50% for each molecule/no significant food effect |
Drug-drug interactions | No unmanageable risk in terms of solid state or PK interactions | No risks in terms of solid state or PK interactions |
Safety and tolerability | Few and manageable drug-related SAEs in phase III and IV | No drug-related SAEs; minimal drug-related AEs that do not result in Study exclusion |
Use in patients with reduced G6PD activity | Testing not required; no enhanced risk in mild-moderate G6PD deficiency | No enhanced risk |
Pregnancy | Not contra-indicated in second or third trimester | Not contra-indicated in second or third trimester, no suggestion of embryo-fetal toxicity in first trimester in preclinical species |
Formulations | Co-formulated tablets or equivalent, with taste-masking for pediatrics if taste is unacceptable to children Long-lasting formulations for intramuscular or intradermal use with low injection volume | Co-formulated tablets for adults. Dispersible or equivalent with taste-masking for pediatrics |
Cost of treatment | ≤$1.00 for adults, $0.25 for infants under 2 years Similar to vaccine costs for an injectable | Idem |
Shelf life of formulated product (ICH guidelines for Zones III/IV; combination only) | ≥2 years | ≥5 years |
Susceptibility to loss of efficacy due to acquired resistance | Very low; no cross resistance with partner | Very low; no cross resistance and orthogonal mechanism from those used in treatment |