Pediatric and Adolescent Endocrinology

MON-228 - Dose Adjustment Strategy for the Long-Acting Growth Hormone Pegpesen Based on IGF-1 Level: A Poppk/PD Simulation Study

Monday, June 15, 2026

9:00 AM - 2:00 PM CT

Location: ENDOExpo; Poster Floor

Senior Author/Primary Investigator(s)

YL

Yan Liang, n/a

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China (People's Republic)

Co-Author(s)

YL

Yan Liang, n/a

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China (People's Republic)
YZ

Youni Zhao, n/a

Xiamen Amoytop Biotech Co., Ltd
Shanghai, China (People's Republic)
FZ

Fenfang Zou, n/a

Xiamen Amoytop Biotech Co., Ltd
Xiamen, China (People's Republic)
YY

Yalin Yin, n/a

Xiamen Amoytop Biotech Co., Ltd
Xiamen, China (People's Republic)
RH

Ruoyi He, n/a

Xiamen Amoytop Biotech Co., Ltd
Xiamen, China (People's Republic)
GG

Ge Ge, n/a

Xiamen Amoytop Biotech Co., Ltd
Chengdu, China (People's Republic)
TL

Tianyi Li, n/a

Xiamen Amoytop Biotech Co., Ltd
Shanghai, China (People's Republic)

Abstract Poster Presenter(s)

Xiaoping Luo, MD, PhD

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China

Senior Author/Primary Investigator(s)

Xiaoping Luo, MD, PhD

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China

Co-Author(s)

Xiaoping Luo, MD, PhD

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China

Disclosure(s):

Xiaoping Luo, MD, PhD: Amoytop: Advisory Board (), Grant Recipient (); GenSci: Advisory Board (), Grant Recipient (), Speakers' Bureau (); Ipsen: Advisory Board (), Grant Recipient (); Kyowa Kirin: Advisory Board (), Grant Recipient (); Lumos: Advisory Board (), Grant Recipient (); Medtronic: Advisory Board (), Grant Recipient (); Novo Nordisk: Advisory Board (), Grant Recipient (), Speakers' Bureau (); Sanofi: Advisory Board (), Grant Recipient (); Takeda: Advisory Board (), Grant Recipient (); Visen: Advisory Board (), Grant Recipient ()

Background and

Objectives: Pegpesen, a novel Y-shaped PEGylated long-acting growth hormone (LAGH), was recently approved in China for pediatric growth hormone deficiency (GHD). Clinical data indicate Pegpesen maintains mean IGF-1 standard deviation scores (SDS) within the ±2.0 range and exhibits a positive dose-response relationship within the 0.14-0.28 mg/kg/week therapeutic window. As IGF-1 SDS is a critical biomarker for monitoring GH therapy, establishing a quantitative dose-response relationship is essential for precision dose titration. Using the 0.14-0.28 mg/kg/week range as the simulation basis, this study aims to characterize the quantitative relationship between Pegpesen dose adjustments and IGF-1 SDS changes via a population pharmacokinetic/pharmacodynamic (PopPK/PD) model to provide evidence-based clinical guidance.

Methods: Data were pooled from a Phase 1 (36 healthy adult males) and Phase 2/3 (292 children with GHD) studies. A PopPK/PD model was developed using a sequential modeling approach in NONMEM (v7.5.0) with the first-order conditional estimation with interaction (FOCEI) method. The model was built upon a robust dataset comprising 2,655 PK and 2,466 IGF-1 PD observations. IGF-1 dynamics were characterized by an indirect response model. Steady-state IGF-1 SDS levels were simulated across three dose levels (0.14, 0.21, and 0.28 mg/kg/week) to quantify the impact of dose effects.

Results: The PopPK/PD model effectively simulated steady-state IGF-1 SDS levels across the therapeutic dose range, demonstrating a strong linear correlation between the Pegpesen dose and pharmacodynamic response. Estimated mean steady-state IGF-1 SDS values were were 0.24, 0.99, and 1.75 for weekly doses of 0.14, 0.21, and 0.28 mg/kg/week, respectively, confirming that IGF-1 levels remain within a safe and effective range throughout the dose spectrum. Model-based simulations quantified the titration strategy: a dose adjustment of 0.01 mg/kg/week is projected to shift the IGF-1 SDS by ±0.11, whereas a 0.02 mg/kg/week adjustment results in a ±0.21 change. Specifically, achieving a target shift of 0.5 in IGF-1 SDS requires a dose adjustment of 0.05 mg/kg/week, providing a quantitative framework for individualized dose titration in clinical practice.

Conclusions: This PopPK/PD analysis establishes a quantitative framework for Pegpesen dose titration. By quantifying the dose-IGF-1 SDS relationship, clinicians can individualize therapy based on current IGF-1 response to reach target levels, ensuring both optimal growth efficacy and safety in children with GHD. These findings offer practical clinical guidance to optimize treatment outcomes.

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