PEGylated weekly rhGH promising in idiopathic short stature

medwireNews: A weekly injectable PEGylated recombinant human growth hormone (PEG-rhGH) gives significantly better height outcomes than no treatment in children with idiopathic short stature (ISS), shows a phase 2 trial.

The weekly PEG-rhGH is currently available only in China, having previously undergone trials in Chinese children with growth hormone deficiency.

The researchers explain that PEG-rhGH consists of a 40 kDa hydrophilic polyethylene glycol (PEG) residue attached to rhGH, giving it “an extended half-life and reduced antigenicity and immunogenicity”.

The current phase 2 trial, published in the European Journal of Endocrinology, involved 360 children who had a height standard deviation score (SDS) below –2.0 (average –2.48) but no clear cause for their short stature. They were an average age of 5.4 years and 63% were boys.

During 52 weeks of treatment, children randomly assigned to receive high-dose PEG-rhGH (0.2 mg/kg per week) had an average height SDS increase of 0.98, and those given the lower dose (0.1 mg/kg per week) had an average 0.56 increase.

By contrast, children in the untreated control group had an average 0.20 gain in height SDS, giving 0.78 and 0.36 differences in height SDS change in favour of high-dose and low-dose PEG-rhGH, respectively.

Children given PEG-rhGH achieved an average height velocity of 10.04 and 8.02 cm/year with the high and low doses, respectively, which were both significantly greater than the 6.13 cm/year in the control group.

Levels of insulin-like growth factor (IGF)-1 were increased in children given PEG-rhGH throughout the study, at average levels of 235 and 172 ng/mL in the high- and low-dose groups, respectively, at week 52, compared with 124 ng/mL in the controls.

Xiaoping Luo (Huazhong University of Science & Technology, Wuhan, China) and study co-authors note that 33.3% and 8.8% of children given the high and low doses, respectively, had an IGF-1 SDS greater than +2.0.

“This observation was comparable with the 42.5% of patients who experienced IGF-1 SDS > +2 in a recent study on the efficacy and safety of daily rhGH in ISS”, they say.

They highlight that IGF-1 levels were generally measured 5–7 days following administration of PEG-rhGH, after their peak at day 2.

The rate of adverse events was similar in all three groups of children and there was no indication of a dose–response relationship between PEG-rhGH and adverse reactions. However, the researchers highlight eyelid swelling in two patients and lipoatrophy in three, which they say were not observed in previous phase 2 trials.

“While the mechanism of lipoatrophy with long-acting rhGH is not known, it could be prevented by avoiding multiple injections at the same site”, they suggest.

The team concludes that the ongoing extension phase of the trial “will provide evidence on the long-term efficacy and safety of PEG-rhGH.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Eur J Endocrinol 2022; 187: 709–718
Martin Savage
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