ESPE Yearbook of Paediatric Endocrinology

Brief summary: This is the first multi-national phase 2 dose finding trial aimed at investigating efficacy and safety of the long acting GH (Somapacitan) with daily GH in short children born SGA. 62 GH treatment-naïve short children born SGA were enrolled in the study. Efficacy was valuated with estimated mean annualized height velocity (HV) after 26 weeks of follow-up. Somapacitan showed similar efficacy of daily rhGH. The study will be extended for further 4 years in order to investigate the long-term efficacy and safety profile.

Somapacitan is a long acting human GH (LAGH) approved for treatment of adults with growth hormone deficiency (GHD). It has a longer half-life than rhGH due to its bond to a small non-covalent albumin-binding moiety that facilitates connection with endogenous albumin thus slowing down drug elimination (1–3). SGA children treated with rhGH have a sub-optimal growth response often due to low adherence to treatment, being daily rhGH therapy burdensome for patients and caregivers (3,4).

REAL5 was a dose-finding, randomised, multi-national, open-label, 5-arm design, controlled phase 2 study investigating the efficacy and tolerability of weekly Somapacitan compared with daily rhGH therapy in a cohort of GH treatment-naïve prepubertal short children born SGA. Sixty-two patients were randomized 1:1:1:1 to receive Somapacitan 0.16 mg/kg/week, Somapacitan 0.20 mg/Kg/week, Somapacitan 0.24 mg/kg/week, rhGH 0.035 mg/kg/day and rhGH 0.067 mg/kg/day for 26 weeks. In total, 61/62 children completed the study. After 26 weeks, HV increased in a dose-dependent manner and resulted 8.9, 11.0, 11.3, 10.3, 11.9 cm/yr respectively in the aforementioned groups. Somapacitan showed similar tolerability and safety of daily rhGH. No serious adverse effects (AE) were reported in the treatment groups and no AEs led to treatment discontinuation.

These results suggest that Somapacitan may be considered in the treatment of short children born SGA as an alternative to rhGH to reduce the burdensome of chronic therapy thus improving the adherence and, consequently, the growth outcome of treatment.

References: 1. Desrosiers P, O’Brien F, Blethen S. Patient outcomes in the GHMonitor: the effect of delivery device on compliance and growth. Pediatr Endocrinol Rev. 2005 Feb;2 Suppl 3:327–31. PMID: 16456500. 2. Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, Rogol A. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the growth hormone research society. J Clin Endocrinol Metab. 2007;92(3):804–810. https://doi.org/10.1210/jc.2006-2017. 3. Battelino T, Rasmussen MH, De Schepper J, Zuckerman-Levin N, Gucev Z, Sävendahl L, NN8640-4042 Study Group. 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. https://doi.org/10.1111/cen.13409.