IGF-1 Assessment During Weekly Somatrogon Treatment in Pediatric Patients With GH Deficiency.

Abstract

Context: In patients with GH deficiency (GHD) receiving GH treatment, IGF-1 concentrations are used by physicians to monitor treatment safety and efficacy and guide dosing decisions. Somatrogon is a long-acting GH approved as a once-weekly treatment for pediatric GHD. Somatrogon administration results in characteristic changes in the IGF-1 profile, with values measured at 96 hours postdose representing mean IGF-1 concentrations that best reflect overall somatrogon exposure.

Objective: To develop a simple method to enable physicians to predict mean IGF-1 concentrations following somatrogon dosing, based on a single IGF-1 measurement taken at any point during the 7-day dosing interval.

Methods: Data from phase 2 and phase 3 somatrogon studies were used to develop a 2-compartment pharmacokinetic model with delayed first-order absorption. An indirect-response pharmacokinetic/pharmacodynamic model was applied to the predicted somatrogon concentrations, and model simulations were used to predict IGF-1 and IGF-1 SD score (SDS) levels for participants in both studies.

Results: A total of 16,213 dosing records (from 42 and 109 participants in the phase 2 and 3 studies, respectively) were used for the simulations, generating predicted values for IGF-1 and IGF-1 SDS. Predicted values were scaled against the respective values at 96 hours (day 4). These values were used to create a table showing the adjustments required to predict mean IGF-1 and IGF-1 SDS values depending on time after dose.

Conclusion: We developed a simple method enabling physicians to predict mean weekly IGF-1 values using IGF-1 values measured at any point in the dosing interval.