Table 2 TPP for an injectable prophylactic medicine for malaria
Parameter to be clinically evaluated for the combination | Minimum essential | Ideal |
|---|---|---|
Antimalarial effects | Blood schizonticides with at least one molecule also having causal prophylactic activity (killing hepatic schizonts) | Both molecules should have causal prophylactic, blood schizonticidal and transmission-blocking activities |
Mechanism of action | Two partner drugs without cross resistance | Two partner drugs have different modes of action, so no cross resistance |
Dosing regimen | Once per month, intramuscular, with an acceptable injection volume | Once per 3Â months, intramuscular or sub-cutaneous with an acceptable injection volume |
Rate of onset of action | Protection, within 72Â h of initial injection | Immediate protection (no lag prior to onset of action) |
Clinical efficacy | ≥ 80% protective efficacy | ≥ 95% protective efficacy: reduction in incidence of symptomatic malaria No drug-resistant parasites identified in volunteer infection studies still capable of transmission |
Drug–drug interactions | No unmanageable risk in terms of solid state or PK interactions | No risks in terms of solid state or PK interactions with other co-administered PrEP or therapeutics |
Safety and tolerability | No drug-related SAEs; minimal drug-related AEs—i.e., not resulting in clinical study exclusion. No unacceptable pain, irritability of inflammation at injection site, especially injection abscesses | Idem |
Use in patients with reduced G6PD activity | Testing not required as no enhanced risk in mild-moderate G6PD deficiency | Testing not required as drugs not linked to haemolytic risk |
Use in infants/children | Use in children > 6 months old | Use in infants, children and adults |
Formulations | Suitable for intramuscular injection with minimal preparation; maximum volume of 2 mL for adults and 0.5 mL for infants, administered with 27 gauge needle; partner drugs can be injected separately | Liquid pre-filled injection device for intramuscular; maximum volume of 1 mL for adults and < 0.5 mL infants administered with 27–30 gauge needle; fixed dose combination of the drugs; or subcutaneous injection if volumes smaller than above for intramuscular injection |
Cost of treatment | < 5 USD per injection | ≤ USD 1 for infants, USD 2 for children, USD 4 for adults |
Shelf life of formulated product (ICH guidelines for zones/IVb) | ≥ 2 years | ≥ 3 years |