Original article · Population modeling
Optimizing Pegpesen dosing with PopPK/PD simulation
This page summarizes a peer-reviewed modeling study that uses Phase 1–3 Pegpesen data to simulate dose up-titration and weight-banded dosing in pediatric growth hormone deficiency (GHD). It is a scientific companion to the registrational trial summaries on the Trials page—not a substitute for local product information or individualized medical decisions. The Phase II Frontiers 2022 article covers the 12-week dose-ranging PK/PD cohort under the same trial ID.
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Publication details
- Title: Optimization of dosing regimens for the long-acting growth hormone pegpesen: A population PK/PD modeling approach
- Journal: Journal of Endocrinological Investigation (2026) 49:599–607
- DOI: 10.1007/s40618-025-02749-4
- Published online: 5 November 2025
- Authors: Youni Zhao, Fenfang Zou, Jianbo Gu, Ruoyi He, Yalin Yin (Xiamen Amoytop Biotech Co., Ltd.)
- Funding: Sponsored by Xiamen Amoytop Biotech Co., Ltd.
- Conflict of interest: All authors are employees of Amoytop.
At a glance
Why this research was done
Long-acting growth hormone (LAGH) reduces injection frequency, but real-world challenges remain: growth velocity can decline over time on fixed doses, and purely weight-based dosing requires frequent recalculation as children grow. The paper argues that dose up-titration may offset GV waning (as suggested for daily rhGH dose–response), and that weight-banded fixed strengths could simplify practice if PK/PD remain equivalent within a narrow band.
Methods (condensed)
Software
- NONMEM v7.5.0 (FOCEI estimation)
- PsN v4.8.1 · R v4.1.3 for EDA and graphics
Data sources
- Phase 1 healthy adults: NCT01339182
- Phase 2/3 pediatric GHD: NCT04513171
- Sequential PopPK, then PopPK/PD (IGF-1 dynamics; GV linked to exposure)
Simulations extended strategies in a virtual cohort context (including literature-based Chinese growth references for weight-banded scenarios, per the paper). Five hundred simulation replicates were used for weight-banded PK, IGF-1 SDS, and GV predictions.
Strategy 1 — Stepwise dose up-titration
Starting dose 0.14 mg/kg once weekly; every 3 months the weekly dose was increased by one of three proportional steps until a maximum of 0.28 mg/kg/week:
- +12.3% per step — reaches 0.28 mg/kg/week in 18 months, then held through 24 months.
- +18.9% per step — reaches target in 12 months.
- +26.0% per step — reaches target in 9 months.
Primary readouts included 12- and 24-month annualized GV, IGF-1 and IGF-1 SDS, and PK/PD profiles.
Up-titration simulation results
| Escalation rate (every 3 mo.) | GV baseline cm/year |
GV month 12 cm/year |
GV month 24 cm/year |
IGF-1 SDS > +2 at 12 mo. | IGF-1 SDS > +2 at 24 mo. | Mean IGF-1 SDS at 12 mo. | Mean IGF-1 SDS at 24 mo. |
|---|---|---|---|---|---|---|---|
| 12.3% | 3.57 (1.06) | 9.51 (2.35) | 9.35 (2.16) | 4.5% | 10.6% | 0.37 (0.75) | 0.82 (0.78) |
| 18.9% | 3.57 (1.06) | 9.85 (2.34) | 9.35 (2.16) | 7.5% | 10.6% | 0.67 (0.75) | 0.82 (0.78) |
| 26.0% | 3.57 (1.06) | 9.88 (2.35) | 9.35 (2.16) | 8.6% | 10.6% | 0.73 (0.76) | 0.82 (0.78) |
Interpretation (authors): Faster escalation produced higher modeled GV at 12 months, but by 24 months all arms converged at 9.35 cm/year, suggesting dose–response saturation. IGF-1 SDS > +2 reached 10.6% in all groups at month 24—aligned with similar GV. The paper notes GV attenuation from year 1 to year 2 was only about 1.7–5.4% under titration, versus larger declines reported for some other LAGH year-on-year. Cost-effectiveness and clinical validation are flagged as open questions.
Strategy 2 — Weight-banded fixed doses
For each marketed strength (2, 2.5, 3, 3.5, 4, 4.5, 5 mg), the manuscript defines a target weight = fixed dose ÷ 0.14 (mg/kg/week reference). Simulations compared exact weight-based dosing to bands of ±1.78 kg and ±3.57 kg around that target (±3.57 kg equals ±2 kg in the paper’s mg/kg framing).
| Fixed dose (mg) | Target weight (kg) | −3.57 kg | −1.78 kg | +1.78 kg | +3.57 kg |
|---|---|---|---|---|---|
| 2 | 14.29 | 10.72 | 12.51 | 16.07 | 17.86 |
| 3 | 21.43 | 17.86 | 19.65 | 23.21 | 25.00 |
| 4 | 28.57 | 25.00 | 26.79 | 30.35 | 32.14 |
| 5 | 35.71 | 32.14 | 33.93 | 37.49 | 39.28 |
Findings: PK exposure and steady-state IGF-1 SDS prediction intervals for exact mg/kg and ±1.78 kg bands largely overlapped; the ±3.57 kg band diverged more. Simulated week-12 GV was similar for exact dosing versus ±1.78 kg, with differences shrinking at higher strengths (see Table 4 in the PDF). Authors conclude that, at 0.14 mg/kg/week, each strength may suit children within about ±1.78 kg of the target weight without materially compromising modeled efficacy or safety.
Context from the discussion
- Pegpesen’s clinical dose–response is described across 0.14–0.28 mg/kg/week, citing registrational and other Amoytop trials; a basket study in ISS, SGA, and Turner syndrome (NCT05838885) is cited with data not yet published in the introduction.
- Simulated GV can run lower than observed clinical GV; the paper stresses using outputs for trends and relative comparisons, not as literal forecasts.
- Conclusions are specific to Pegpesen; extrapolation to other LAGH platforms is discouraged.
Authors’ conclusions (verbatim themes)
How this page relates to the rest of the site
- Labeled dosing remains 0.14 mg/kg once weekly unless your region approves a different regimen.
- Phase III efficacy describes the registrational comparison at 0.14 mg/kg/week versus daily somatropin.
- Molecule & formulation explains the Y-shaped PEGylated construct that underlies the PK profile modeled here.
For medical information or to discuss modeling implications for your market, contact Amoytop medical affairs through the channels listed on Name & composition.