A Novel Y-Shaped Pegylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency

Abstract

Context: Pegpesen is a novel Y-shape pegylated recombinant human growth hormone (rhGH) for once-weekly treatment of children with growth hormone deficiency (GHD).

Objective: This work aimed to evaluate the efficacy and safety of Pegpesen in children with GHD vs daily rhGH.

Methods: A multicenter, randomized, controlled phase 3 clinical trial was conducted at 23 centers in China with a duration of 52 weeks' treatment. There were 391 pediatric participants diagnosed with GHD. Participants were randomly assigned 2:1 to a weekly Pegpesen group (140 μg/kg/week) or a daily rhGH group (245 μg/kg/week) for 52 weeks. The primary end point was the growth velocity (GV) at 52 weeks, and the secondary end points mainly involved changes from baseline in height SD scores for chronological age and bone age (ΔHt SDS CA and ΔHt SDS BA).

Results: At 52 weeks, the least squares mean (LS means) of GV was 9.910 cm/year in the Pegpesen group and 10.037 cm/year in the daily rhGH group. The LS means difference between groups was -0.127 (95% CI, -0.4868 to 0.2332), confirming that weekly Pegpesen is noninferior to daily rhGH. The LS means of ΔHt SDS CA, ΔHt SDS BA, were similar across both groups (all P > .05). Safety profiles and adherence were comparable.

Conclusion: Pegpesen was noninferior to daily rhGH, with similar safety, lower dosage requirements, thus presenting a new therapeutic option for children with GHD.

Keywords: Y-shape pegylated rhGH; growth hormone; growth hormone deficiency; long-acting growth hormone; pediatric.

Figure 1.

Annualized growth velocity (cm/year) by visit (full analysis set). Abbreviations: GV, growth velocity; LSMEAN, least squares mean; rhGH, recombinant human growth hormone.

Figure 2.

Observed IGF-1 SDS and IGFBP-3 profiles following Pegpesen and daily rhGH administration. A, At 52 weeks of treatment, IGF-1 SDS levels significantly improved both in the Pegpesen and daily rhGH groups compared to baseline (both P < .001). P = .0041 for intergroup comparisons. B, IGFBP-3 levels also significantly improved compared to baseline both in the Pegpesen and daily rhGH groups (both P < .001). P = .004 for intergroup comparisons. The statistical difference between the 2 groups was mainly due to different frequency of administration, thus the test results represented trough concentration in the Pegpesen group and peak concentration in the daily rhGH group. Abbreviations: IGF-1, insulin-like growth factor-1; IGFBP-3, insulin-like growth factor-binding protein 3; LSMEAN, least squares mean; rhGH, recombinant human growth hormone; SDS, SD score.

Figure 3.

Quantitative pharmacology results: IGF-1 SDS profiles during 52 weeks after Pegpesen administration in children with GHD simulated by PK/PD model (n = 292). Abbreviations: GHD, growth hormone deficiency; IGF-1, insulin-like growth factor-1; PK/PD, pharmacokinetic/pharmacodynamic; SDS, SD score.