title: Efficacy and safety of a new ready-to-use recombinant human growth hormone solution.
abstract: We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency (GHD) that were paramount to the development of a new recombinant human GH (rh- GH, somatropin), approved as the first 'biosimilar' in Europe. Study 1 consisted of 3 parts performed in 89 children. The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [Somatropin Powder (Sandoz)] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [Somatropin Solution (Sandoz)] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution. Study 2 was performed in 51 children and designed to demonstrate efficacy and safety of Somatropin Powder and to confirm its low immunogenic potential; rhGH was given sc at a daily dose of 0.03 mg/kg. Primary [body height, height SD score (HSDS), height velocity, and height velocity (HV) SD score (HVSDS)] and secondary [IGF-I and IGF binding protein 3 (IGFBP-3)] efficacy endpoints and safety parameters were assessed regularly. In study 1, all treatments showed comparable increases in growth. The baseline-adjusted difference between Somatropin Powder and the reference rhGH product in mean HV was -0.20 cm/yr (95% confidence interval (CI) [-1.34;0.94]) and in mean HVSDS was 0.76 (95% CI [-0.57;2.10]) after 9 months. These very small differences demonstrate comparable therapeutic efficacy between the two treatments. The results of study 2 were consistent with those seen in study 1. Equivalent therapeutic efficacy and clinical comparability in terms of safety and immunogenicity between Somatropin Powder and the reference rhGH product and between Somatropin Powder and Somatropin Solution was demonstrated. The safety and immunogenicity profiles were similar and as expected from experience with rhGH preparations.
authors.affiliation: Department of Endocrinology, Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Romer
authors.forename: F
authors.initials: F
authors.lastname: Peter
authors.forename: P
authors.initials: P
authors.lastname: Saenger
authors.forename: J
authors.initials: J
authors.lastname: Starzyk
authors.forename: B
authors.initials: B
authors.lastname: Koehler
authors.forename: E
authors.initials: E
authors.lastname: Korman
authors.forename: M
authors.initials: M
authors.lastname: Walczak
authors.forename: R
authors.initials: R
authors.lastname: Wasik
authors.forename: M
authors.initials: M
authors.lastname: Ginalska-Malinowska
authors.forename: E
authors.initials: E
authors.lastname: Solyom
authors.forename: A
authors.initials: A
authors.lastname: Berghout
mesh_terms: D000365:Age Determination by Skeleton; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011208:Powders; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012996:Solutions; D016896:Treatment Outcome
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011208:Powders; D011994:Recombinant Proteins; D012996:Solutions; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I