Skip to main content

Advertisement

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 3 months Oral once per month; injectable less frequently than once per 3 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