Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan

Abstract

Context: Somapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration.

Objective: To develop and assess the reliability of linear models for predicting mean and peak IGF-I levels from samples taken on different days after dosing.

Design: A pharmacokinetic/pharmacodynamic model was used to simulate IGF-I data in adults and children following weekly somapacitan treatment of GHD.

Setting and patients: 39 200 IGF-I profiles were simulated with reference to data from 26 adults and 23 children with GHD.

Intervention(s): The simulated dose range was 0.02 to 0.12 mg/kg for adults and 0.02 to 0.16 mg/kg for children. Simulated data with >4 average standard deviation score were excluded.

Main outcome measure(s): Linear models for predicting mean and peak IGF-I levels based on IGF-I samples from different days after somapacitan dose.

Results: Robust linear relationships were found between IGF-I sampled on any day after somapacitan dose and the weekly mean (R2 > 0.94) and peak (R2 > 0.84). Prediction uncertainties were generally low when predicting mean from samples taken on any day (residual standard deviation [RSD] ≤ 0.36) and peak from samples taken on day 1 to 4 (RSD ≤ 0.34). IGF-I monitoring on day 4 and day 2 after dose provided the most accurate estimate of IGF-I mean (RSD < 0.2) and peak (RSD < 0.1), respectively.

Conclusions: Linear models provided a simple and reliable tool to aid optimal monitoring of IGF-I by predicting mean and peak IGF-I levels based on an IGF-I sample following dosing of somapacitan. A short visual summary of our work is available (1).

Keywords: IGF-I; IGF-I SDS; long-acting growth hormone; monitoring; once-weekly dosing.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.

Modeled IGF-I SDS fluctuations over a week demonstrate peak, mean and trough IGF-I levels of weekly somapacitan vs IGF-I levels following daily GH injections in a) children and b) adults. Abbreviations: GH, growth hormone; GHD, growth hormone deficiency; IGF-I, insulin-like growth factor-I.

Figure 2.

Simulated data used as the basis for linearization: individual predicted IGF-I SDS profiles for a) adults and b) children by time (in days) after dose and somapacitan dose. Profiles with an average IGF-I SDS > 4 over a week were excluded. Lines represent mean values. Shaded areas represent 5th to 95th percentiles. Abbreviations: IGF-I, insulin-like growth factor-I; SDS, standard deviation score.

Figure 3.

Correlations between individual predicted IGF-I SDS on days 2 and 4 after somapacitan dosing versus the weekly peak (top panel) and the weekly mean (bottom panel) IGF-I SDS levels for a) adults with GHD and b) children with GHD. The line of identity is shown (in black, dashed line at 45°). Abbreviations: AGHD, adults with growth hormone deficiency; GHD, growth hormone deficiency; IGF-I, insulin-like growth factor-I; SDS, standard deviation score.

Figure 4.

Illustration of the predicted IGF-I SDS profiles and the 90% prediction interval for a sample taken on days 0–7 after somapacitan dosing for a typical a) adult with GHD (2 mg dose of somapacitan) and b) child with GHD (0.16 mg/kg somapacitan). The solid line and shaded area represent the predicted IGF-I SDS profile with a 90% prediction interval based on a single sample (red dot). Abbreviations: GHD, growth hormone deficiency; IGF-I, insulin-like growth factor-I; SDS, standard deviation score.

Figure 5.

Illustration of the impact of somapacitan dose in a) adults (0.1, 1.0, 3.0, and 8 mg) and c) children (0.02, 0.04, 0.08, and 0.16 mg/kg), and of b) body weight in adults (50, 80, and 120 kg) on predicted IGF-I SDS profiles, for a single IGF-I sample. The blue dot indicates the single IGF-I sample in each case. Abbreviations: IGF-I, insulin-like growth factor-I; SDS, standard deviation score.