ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab, 2025, Vol. 110, Issue 4, Pages 1086–1095. PMID: 39271158 doi: 10.1210/clinem/dgae616

Brief Summary: The phase 2 REAL5 study investigated the efficacy, safety, and tolerability of somapacitan, a once-weekly long-acting growth hormone (LAGH) derivative, in prepubertal short children born small for gestational age (SGA), comparing it to conventional daily growth hormone (GH) administration. Somapacitan is a reversible albumin-binding GH derivative approved for once-weekly treatment of GH deficiency (GHD) in adults and children, and is being evaluated as a less burdensome treatment option for other indications, including SGA.

REAL5 is a randomized, multicenter, open-label, controlled phase 2 study. It comprises a 26-week main phase, a 26-week extension, and an ongoing 4-year safety extension. A total of 62 GH-treatment-naïve, prepubertal short children born SGA were randomized, with 61 completing 52 weeks of treatment. Patients were randomized in a 1:1:1:1:1 ratio to receive either:

Somapacitan at doses of 0.16, 0.20, or 0.24 mg/kg/week or daily GH (Norditropin®) at doses of 0.035 or 0.067 mg/kg/day.

A sustained dose-dependent growth response was observed for somapacitan after 52 weeks.

Estimated mean HV at week 52 was 8.5, 10.4, and 10.7 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively. For daily GH, estimated mean HV was 9.3 and 11.2 cm/year for 0.035 and 0.067 mg/kg/day, respectively. Somapacitan 0.24 mg/kg/week demonstrated similar efficacy to daily GH 0.067 mg/kg/day. Dose-dependent increases in total IGF-I and peak IGF-I bioactivity were observed for both treatments and were similar between comparator groups.

Somapacitan was well-tolerated at all doses, with a safety profile consistent with that of daily GH. Only one mild lipoatrophy injection-site reaction was reported in the somapacitan 0.16 mg/kg/week arm after 52 weeks. High adherence was observed across all treatment arms, with mean adherence rates exceeding 94%.

The study concluded that once-weekly somapacitan provides similar efficacy, safety, and tolerability, as well as comparable bioactive and total IGF-I response, as daily GH (specifically, 0.067 mg/kg/day) in children born SGA after 52 weeks of treatment. The somapacitan 0.24 mg/kg/week dose was selected for the ongoing extension phase of the REAL5 study and for recently initiated randomized controlled phase 3 trials (REAL8, REAL9).

These findings suggest that once-weekly somapacitan could represent a favorable and less burdensome treatment option for short children born SGA, potentially improving adherence and clinical outcomes by reducing the frequency of injections from 365 to 52 per year.