Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4

Eur J Endocrinol. 2025 Apr 30;192(5):651-661. doi: 10.1093/ejendo/lvaf096.

Abstract

Objective: Somapacitan is a long-acting GH approved for once-weekly treatment of GH deficiency (GHD). This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD.

Design: Randomized, multi-national, open-labelled, active-controlled parallel-group phase 3 trial, with a 52-week main phase and 3-year safety extension (NCT03811535).

Methods: Treatment-naïve children with GHD were randomized (2:1) to continuous somapacitan (0.16 mg/kg/week; "soma/soma" group) or daily GH (Norditropin®; 0.034 mg/kg/day) followed by somapacitan (0.16 mg/kg/week; "switch" group).

Results: Of 200 participants, 188 completed 3 years of treatment. Sustained growth was observed in both groups. At week 156, mean (SD) height velocity (HV) between weeks 104 and 156 was 7.4 (1.5) cm/year in the soma/soma group and 7.8 (1.4) cm/year in the switch group. At week 156, the soma/soma and switch groups had reached a mean (SD) height SD score (HSDS) of -0.95 (0.98) and -1.08 (0.93), respectively, and were approaching the mean mid-parental HSDS of -0.74 (for both groups). Mean total insulin-like growth factor I (IGF-I) SDS during year 3 was similar between groups and within normal range (-2.0 to +2.0). Bioactive IGF-I and bioactive IGF-I to IGF-I ratio were similar between groups. Somapacitan was well tolerated, with low proportions reporting injection-site reactions.

Conclusions: Sustained efficacy and tolerability were observed for continuous somapacitan treatment for 3 years, and for 2 years after the switching from daily GH treatment. HSDS in both groups was approaching mean mid-parental HSDS.

Clinical trial registration: NCT03811535.

Keywords: growth hormone; growth hormone deficiency; growth hormone replacement therapy; long-acting growth hormone; somapacitan.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adolescent
  • Body Height / drug effects
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Dwarfism, Pituitary* / blood
  • Dwarfism, Pituitary* / drug therapy
  • Dwarfism, Pituitary* / metabolism
  • Female
  • Growth Disorders* / blood
  • Growth Disorders* / drug therapy
  • Growth Disorders* / metabolism
  • Histidine
  • Human Growth Hormone* / administration & dosage
  • Human Growth Hormone* / adverse effects
  • Human Growth Hormone* / deficiency
  • Humans
  • Insulin-Like Growth Factor I* / analysis
  • Insulin-Like Growth Factor I* / metabolism
  • Male
  • Mannitol
  • Phenol
  • Treatment Outcome

Substances

  • Human Growth Hormone
  • IGF1 protein, human
  • Insulin-Like Growth Factor I
  • somapacitan
  • Histidine
  • Mannitol
  • Phenol

Associated data

  • ClinicalTrials.gov/NCT03811535

Grants and funding