| Autor: |
Hershkovitz, Oren, Bar-Ilan, Ahuva, Guy, Rachel, Felikman, Yana, Moschcovich, Laura, Hwa, Vivian, Rosenfeld, Ron G., Fima, Eyal, Hart, Gili |
| Zdroj: |
Molecular Pharmaceutics; February 2016, Vol. 13 Issue: 2 p631-639, 9p |
| Abstrakt: |
MOD-4023 is a novel long-acting version of human growth hormone (hGH), containing the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG). MOD-4023 is being developed as a treatment for adults and children with growth hormone deficiency (GHD), which would require fewer injections than currently available GH formulations and thus reduce patient discomfort and increase compliance. This study characterizes MOD-4023’s binding affinities for the growth hormone receptor, as well as the pharmacokinetic and pharmacodynamics, toxicology, and safety profiles of repeated dosing of MOD-4023 in Sprague–Dawley rats and Rhesus monkeys. Although MOD-4023 exhibited reduced in vitropotency and lower affinity to the GH receptor than recombinant hGH (rhGH), administration of MOD-4023 every 5 days in rats and monkeys resulted in exposure comparable to daily rhGH, and the serum half-life of MOD-4023 was significantly longer. Repeated administration of MOD-4023 led to elevated levels of insulin-like growth factor 1 (IGF-1), and twice-weekly injections of MOD-4023 resulted in larger increase in weight gain with fewer injections and a lower accumulative hGH dose. Thus, the increased half-life of MOD-4023 in comparison to hGH may increase the frequency of protein–receptor interactions and compensate for its decreased in vitropotency. MOD-4023 was found to be well-tolerated in rats and monkeys, with minimal adverse events, suggesting an acceptable safety profile. These results provide a basis for the continued clinical development of MOD-4023 as a novel treatment of GHD in children and adults. |
| Databáze: |
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