Preclinical Investigations of a Novel PEGylated Long-Acting Human Growth Hormone
Year: 2025
Type: article
Abstract: Jun Wang,1,2 He Wang,1,2 Rong Wang,1,2 Yu Zhuang,1,2 Chenyang Jiang,1,2 Baixue Zhao,1,2 Zhen Xu,1,2 Bruce Yong Ma1,2 1Zonhon Biopharma Institute, Inc., Changzhou, Jiangsu, People’s Republic of China; 2Jiangsu Engineering Research Center for Precision Biomedicines, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Bruce Yong Ma, Zonhon Biopharma Institute, Inc., 518 Yunhe Road, Xinbei District, Changzhou, Jiangsu, 213125, People’s Republic of China, Tel +86-0519-81881825, Email [email protected]: The daily administration of recombinant human growth hormone (rhGH) replacement therapies via subcutaneous (SC) injections can be burdensome for patients. Long-acting Growth hormone (GH) formulation could reduce injection frequency, and it will be expected to increase treatment adherence. ZHB111 is a PEGylated rhGH that requires sc injection every two weeks. This study aims to examine the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of multiple sc doses of ZHB111.Design and Methods: In the PK study, naïve cynomolgus monkeys were divided into four groups with 3/sex/group. Each group received single subcutaneous administration at 0 (control article, Sodium chloride injection), 0.3, 1.0 and 3.0 mg/kg, respectively. To access safety and PD profile, cynomolgus monkeys were randomly assigned to 4 groups of 5/sex/group, and were dosed with ZHB111 once weekly for 4 times by subcutaneous injection at 0 (control article, Sodium chloride injection), 1, 5 or 20.6 mg/kg/dose. Tissue distribution was accessed by administering a single subcutaneous dose of ZHB111 to Sprague-Dawley Rats.Results: ZHB111 exhibits a significant difference in serum half-life (in monkeys) across varying dosages, with a trend of decreasing half-life as the dosage increases, ranging from 110– 30 h. No significant differences were observed between different genders at the same dosage level. After subcutaneous administration of 0.3mg/kg of ZHB111, the mean values of IGF-1 in male animals ranged among 594.93~1294.98ng/mL at various time points, while those in female animals were within the range of 394.15~770.01ng/mL.Conclusion: The tolerability of ZHB111 was demonstrated in both rat and monkey models, with only minimal adverse effects observed. These findings support the continued clinical development of ZHB111 as a novel treatment for growth hormone deficiency (GHD) in both children and adult patients.Keywords: long-acting, growth hormone, PEGylated, growth hormone deficiency, GHD
Authors: Wang J, Wang H, Wang R, Zhuang Y, Jiang C, Zhao B, Xu Z, Ma BY
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6986570933
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