Population Pharmacokinetic and Exposure‐Efficacy Analysis of Baloxavir Marboxil for Influenza Treatment and Post‐Exposure Prophylaxis in Children

Baloxavir acid (baloxavir), the active metabolite of the prodrug baloxavir marboxil, is a selective inhibitor of the influenza virus cap‐dependent endonuclease. The population pharmacokinetic (popPK) profile of baloxavir in adults/adolescents has been described previously. To characterize the PK of baloxavir in patients aged ≥1 year, a popPK model was developed using data from 1,795 patients across six studies, including miniSTONE‐2 (NCT03629184) in which children aged 1 to <12 years received a bodyweight‐based single oral dose of baloxavir marboxil (2 mg/kg, <20 kg; 40 mg, ≥20 kg) for treatment of influenza. The final popPK model was a 2‐compartment model with first‐order absorption and elimination processes and an absorption lag time; the most influential covariates affecting baloxavir exposure were bodyweight and race (Asian versus non‐Asian). Pediatric‐to‐adult exposure matching for PK parameters relevant for treatment and post‐exposure prophylaxis (PEP) indications were used to support pediatric label extensions. Adequate exposure matching was demonstrated between non‐Asian pediatric patients using the miniSTONE‐2 dose and non‐Asian adult patients. After dosing optimization, predicted baloxavir exposures in Asian pediatric patients using the miniSTONE‐2 dose were similar to exposures in Asian adults. To bridge PEP efficacy data from the BLOCKSTONE study in Japanese pediatric patients (JapicCTI‐184,180) to non‐Asian patients aged ≥1 year, an exposure‐matching approach between Japanese pediatric patients receiving the lower BLOCKSTONE dose and non‐Asian pediatric patients receiving the miniSTONE‐2 dose was employed. Together, these observations indicate that the recommended miniSTONE‐2 dosing regimen is likely to be efficacious for treatment and PEP in children aged 1–<12 years, regardless of race.