Rasmus J Kildemoes, Philippe F Backeljauw, Michael Højby, Joanne C Blair, Bradley S Miller, Jun Mori, Yassine K Lyauk
Journal of the Endocrine Society, Volume 7, Issue 11, November 2023, bvad115
https://doi.org/10.1210/jendso/bvad115
Growth hormone (GH) replacement therapy improves longitudinal growth and adult height in children with GH deficiency (GHD). GH stimulates insulin-like growth factor (IGF)-I release, the biomarker used for monitoring GH activity during treatment.
This study aims to provide model-based insights into the dose–IGF-I responses of once-weekly somapacitan, a novel long-acting GH, compared with daily GH in children with GHD.
Analyses included dosing information and 1473 pharmacokinetic samples from 210 somapacitan-treated pediatric patients with GHD across 3 trials, including phase 1 (NCT01973244), phase 2 (NCT02616562; REAL 3), and phase 3 (NCT03811535; REAL 4), as well as 1381 IGF-I samples from 186 patients with GHD treated with somapacitan in REAL 3 and REAL 4. Pharmacokinetic/pharmacodynamic modeling to characterize somapacitan dose–IGF-I response and predict the response to dosing day changes.
Relationships were established between somapacitan dose, exposure, change from baseline IGF-I SD score (SDS), and height velocity (HV). A linear model permitted the development of a tool to calculate estimated average weekly IGF-I exposure from a single IGF-I sample obtained at any time within the somapacitan dosing interval at steady state. In practice, the use of this tool requires knowledge of somapacitan injection timing relative to IGF-I sample collection timing. IGF-I SDS simulations support flexible dosing day changes while maintaining at least 4 days between doses.
We characterized the dose–IGF-I response of somapacitan in children with GHD. To support physicians in IGF-I monitoring, we present a practical guide about expected weekly average IGF-I concentrations in these patients and provide insights on dosing day flexibility.
We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.