Optimization of dosing regimens for the long-acting growth hormone pegpesen: A population PK/PD modeling approach

TL;DR

This study uses modeling to find better dosing strategies for a long-acting growth hormone in children with growth hormone deficiency.

Contribution

The study introduces optimized dosing strategies for Pegpesen using population PK/PD modeling to improve growth outcomes in GHD children.

Findings

Dose up-titration improved growth velocity in the first year but plateaued by the second year.

Weight-banded dosing within ±1.78 kg of target weight showed comparable efficacy to standard dosing.

IGF-1 levels remained within safe ranges with the optimized strategies.

Abstract

Long-acting growth hormone (LAGH) provides a convenient treatment for children with growth hormone deficiency (GHD), but challenges such as waning growth velocity (GV) and dosing inflexibility persist. This study aimed to explore optimized dosing strategies for Pegpesen, a novel LAGH, using population pharmacokinetic/pharmacodynamic (PopPK/PD) modeling to improve therapeutic outcomes.

A PopPK/PD model was developed using data from Phase 1–3 trials of Pegpesen. Two strategies were simulated in 292 GHD patients: (1) Dose up-titration, starting at 0.14 mg/kg/week and increasing by 12.3%, 18.9%, and 26.0% every 3 months to a maximum of 0.28 mg/kg/week. (2) Weight-banded dosing, evaluating the suitability of fixed doses for children within ± 1.78 kg and ± 3.57 kg of a target weight (fixed dose/0.14 kg). Primary evaluation metrics included 12- and 24-month GV, IGF-1 levels, and PK/PD profiles.

The up-titration strategy dose-dependently increased 12-month GV (9.51–9.88 cm/year), which then converged by 24 months, suggesting that saturation was reached before the second year of treatment. IGF-1 levels remained within safe range. For weight-banded dosing, PK/PD profiles for subjects within ± 1.78 kg of the target weight were comparable to standard weight-based dosing, whereas profiles for the ± 3.57 kg range showed significant divergence.

This PopPK/PD model for LAGH Pegpesen in GHD children proposes a dose up-titration regimen that effectively counteracts declining GV while maintaining safety, and a simplified weight-banded dosing system that enhances treatment convenience without compromising efficacy.

The online version contains supplementary material available at 10.1007/s40618-025-02749-4.

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