An open-label extension of a phase 2 dose-finding study of once-weekly somatrogon vs. once-daily Genotropin in children with short stature due to growth hormone deficiency: results following 5 years of treatment

J Pediatr Endocrinol Metab. 2023 Feb 3;36(3):261-269. doi: 10.1515/jpem-2022-0359. Print 2023 Mar 28.

Abstract

Objectives: Somatrogon is a long-acting recombinant human growth hormone (GH) employed as a once-weekly treatment for children with GH deficiency (GHD). A 12-month, phase 2 study of once-weekly somatrogon vs. once-daily GH (Genotropin®) was initiated, after which participants could enroll into an open-label extension (OLE) evaluating the safety and efficacy of long-term somatrogon treatment.

Methods: There were five study periods, Periods I and II were 6 months each while Periods III, IV, and V were 12 months each. In the main study (Periods I and II), 53 prepubertal children with GHD were randomized to once-weekly somatrogon (0.25, 0.48, or 0.66 mg/kg/week) or once-daily Genotropin (0.034 mg/kg/day); 48 continued into the OLE, consisting of Period III (original somatrogon dose; Genotropin recipients randomized to one of three somatrogon doses), Period IV (somatrogon 0.66 mg/kg/week), and Period V (prefilled somatrogon pen [0.66 mg/kg/week]).

Results: At the end of Period III, the mean ± SD annual height velocity (HV) for 0.25, 0.48, and 0.66 mg/kg/week somatrogon groups was 7.73 ± 1.89, 7.54 ± 1.28, and 8.81 ± 1.12 cm/year, respectively; HV was sustained during Periods IV/V. Height SD scores (SDS) showed progressive improvement throughout the OLE, regardless of initial cohort assignment, approaching the normal range (-0.69 ± SD 0.87) at the end of Period V Year 1. Mild or moderate treatment-emergent adverse events were reported in 81.3% of participants, most unrelated to study drug.

Conclusions: Up to 5 years of once-weekly somatrogon was well tolerated and resulted in sustained improvement in height SDS and delta height SDS in prepubertal short children with GHD.

Keywords: Genotropin; IGF-1; children; growth hormone; growth hormone deficiency; height velocity; long-acting growth hormone; pediatric; somatrogon; somatropin.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Body Height
  • Child
  • Dwarfism, Pituitary* / drug therapy
  • Growth Disorders / drug therapy
  • Growth Hormone / therapeutic use
  • Human Growth Hormone*
  • Humans
  • Insulin-Like Growth Factor I / therapeutic use

Substances

  • Human Growth Hormone
  • somatrogon
  • Insulin-Like Growth Factor I
  • Growth Hormone