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

Area of Science:

• Endocrinology
• Pharmacokinetics
• Pediatric Growth Disorders

Background:

• Insulin-like Growth Factor 1 (IGF-1) monitoring is crucial for assessing the safety and efficacy of Growth Hormone (GH) treatment in patients with GH deficiency (GHD).
• Somatrogon, a long-acting GH therapy for pediatric GHD, requires careful IGF-1 level assessment.
• IGF-1 levels measured 96 hours postdose best represent mean somatrogon exposure.

Purpose of the Study:

• To develop a straightforward method for predicting mean IGF-1 concentrations after somatrogon administration.
• To enable prediction using a single IGF-1 measurement taken at any point within the 7-day dosing interval.

Main Methods:

• Utilized data from Phase 2 and 3 somatrogon studies.
• Developed a 2-compartment pharmacokinetic model with delayed first-order absorption.
• Applied an indirect-response pharmacokinetic/pharmacodynamic model and simulations to predict IGF-1 and IGF-1 standard deviation scores (SDS).

Main Results:

• Simulations involved 16,213 dosing records from 151 participants.
• Predicted IGF-1 and IGF-1 SDS values were scaled against 96-hour postdose measurements.
• A table was created to guide adjustments for predicting mean IGF-1 and IGF-1 SDS based on the time of measurement.

Conclusions:

• A simplified method has been developed to predict mean weekly IGF-1 values.
• This method allows for accurate prediction using IGF-1 measurements taken at any time during the dosing interval.