Endocrine Abstracts

Somapacitan is a long-acting growth hormone (GH) intended for once-weekly subcutaneous administration. As for GH, the mechanism of action of somapacitan is either directly or indirectly via insulin-like growth factor I (IGF-I). A PK/PD model of somapacitan was developed from the pharmacokinetics (PK) and IGF-I levels from three phase 1 trials data: a single dose/multiple dose trial (0.02–0.24 mg/kg per week) in healthy adults, a multiple dose trial in adults with growth hormone deficiency [GHD] (0.02–0.12 mg/kg perweek) and a single dose trial in children with GHD (0.02–0.16 mg/kg). Somapacitan exposure-response was described with a non-linear relationship between dose and exposure and a delay in response observed between C_max PK and C_max IGF-I. Somapacitan PK levels and IGF-I response was found to correlate to body weight bridging exposure and response between children and adults. The PK/PD model was based on goodness of fit judged adequate to describe somapacitan exposure and IGF-I levels and simulate the expected IGF-I profiles after multiple doses in children. Descriptive IGF-I exposure-response analysis of single dose data in GHD paediatric patients indicated that the dose range 0.04–0.16 mg/kg provided change in IGF-I comparable to daily hGH. Based on the PK/PD model of somapacitan, once-weekly dosing of 0.04 mg/kg per week are expected to provide C_max IGF-I levels that match the average daily human GH (hGH) treatment; 0.08 mg/kg per week are expected to provide C_avg IGF-I levels that match the average daily hGH treatment; and 0.16 mg/kg per week are expected to provide higher IGF-I levels than with daily hGH, with average concentrations not exceeding +2 SDS. In conclusion, the PK/PD of somapacitan is well characterised in adults and children in GHD in support of once-weekly dosing.