ESPE Yearbook of Paediatric Endocrinology

Brief summary: This multicenter, randomized, controlled, phase 3 study compared the effects of long-acting GH (Somapacitan; 0.16 mg/kg/wk) with daily GH (Norditropin; 0.034 mg/kg/d), in GHD children. The trial was conducted over 52 weeks, followed by an ongoing 3-year single-group extension period. Similar efficacy and safety for somapacitan compared to daily GH was demonstrated over 52 weeks of treatment.

Long-acting growth hormone (LAGH) formulations have been under intense investigation in the last decades for improving adherence to chronic GH therapy in both children and adults with GHD.

Somapacitan, a once-weekly reversible albumin-binding GH derivative, has been approved for the treatment of adults in Europe, United States and Japan and trials in GHD children are ongoing (1).

A previous phase 2 dose-finding and safety trial in prepubertal children with GHD showed that 0.16 mg/kg/wk Somapacitan had the same efficacy and safety profile of daily GH treatment (0.034 mg/kg/d) over 3 years of treatment (2).

In this phase 3 REAL4 trial, the authors aimed at evaluating the efficacy, safety, and tolerability of once-weekly Somapacitan 0.16 mg/kg/wk compared with daily GH in prepubertal, treatment-naïve children with GHD. Efficacy estimates were height velocity (HV; cm/y) at week 52 and changes from baseline to end in height SDS (HSDS), HVSDS, IGF-I SDS, and bone age. Incidence of adverse events (AEs), occurrence of anti-somapacitan and anti-GH antibodies, changes in laboratory parameters, including lipid profile, glucose, insulin, and glycated hemoglobin level, were assessed as safety endpoints.

Efficacy of Somapacitan was confirmed by mean HV after 52 weeks of treatment (11.2 cm/y for Somapacitan and 11.7 cm/y for daily GH). HVSDS and HSDS increased from baseline to week 52 for both Somapacitan and daily GH, with non-statistically significant differences between treatment groups.

Mean IGF-I SDS values at week 52 and change in mean IGF-I SDS from baseline to week 52 were similar between treatment groups. IGF-I SDS increased after Somapacitan injection to an estimated mean peak of +1.7 SDS after an average time of 58 hours. Thereafter, the profile declined to a mean pre-dose IGF-I of −0.8 SDS.

In conclusion, noninferiority in HV for somapacitan compared with daily GH was demonstrated with similar safety and mean IGF-I SDS in treatment-naïve children with GHD.

References: 1. Battelino, T., et al., Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: A randomized dose-escalation trial. Clin Endocrinol (Oxf). 2017;87(4):350–358. 2. Sävendahl L, Battelino T, Højby Rasmussen M, Brod M, Saenger P, Horikawa R. Effective GH Replacement With Once-weekly Somapacitan vs Daily GH in Children with GHD: 3-year Results From REAL 3. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1357–1367. doi: 10.1210/clinem/dgab928. PMID: 34964458; PMCID: PMC9016428.