ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab ;105(4):e1847–e1861.

The REAL 3 multicenter randomized, controlled, double-blind phase 2 study evaluated the efficacy and safety of different doses of once-weekly Somapacitan, compared to conventional once-daily GH in 59 prepubertal GHD children. The treatment period lasted 26 weeks and an additional extension to 52 weeks. At week 26, height velocity (HV) was 7.8, 10.9 and 13.1 cm/year, respectively, for the three increasing doses of Somapacitan (0.04, 0.08 and 0.16 mg/kg per week) compared to 11.4 cm/year on daily GH (0.034 mg/kg per day). The corresponding HV at 52 weeks were 7.5, 9.7 and 11.7 cm/year for Somapacitan, and 9.9 cm/year for daily GH. Similar effects of the different treatment regimens were observed on heights gain from baseline. The Somapacitan dose 0.16 mg/kg per week was considered to have an efficacy overlapping that of conventional daily GH. A PK/PD model used to derive individual IGF-I profiles and IGF-I average levels showed that Somapacitan 0.16 mg/kg per week provided IGF-I levels equivalent to daily GH. No major side effect was reported and the overall safety profile was not different among the treatment groups.

Recombinant human (rhGH) therapy, by daily subcutaneous injection, is currently used to improve linear growth and, ultimately, adult height, in a wide range of conditions associated with short stature. Clinical responses to GH therapy are variable, influenced by factors such as the underlying diagnosis, GH dose, age at start of treatment, parental heights, and adherence to therapy (1). Poor adherence to therapy may be a major issue, eventually affecting adult height. The prevalence of non-adherence to GH in childhood seems to be extremely variable, ranging from 5 to 82% in different populations (1) (2).

Long-acting (LA) GH formulations were developed to improve adherence to GH therapy and reduce the its burden to patients and families. Somapacitan is a once-weekly modified rhGH containing a fatty acid with non-covalent albumin-binding properties, which prolongs the half-life and thus its duration of action. This LAGH formulation has been shown to be well tolerated, safe and effective in GHD adults (3). The current trial confirms its efficacy and short-term safety in GHD children.

References:

1. Acerini CL, Wac K, Bang P, Lehwalder D. Optimizing Patient Management and Adherence for Children Receiving Growth Hormone. Front Endocrinol (Lausanne). 2017;8:313.

2. Miller BS, Velazquez E, Yuen KCJ. Long-Acting Growth Hormone Preparations – Current Status and Future Considerations. J Clin Endocrinol Metab. 2020;105(6).

3. Johannsson G, Feldt-Rasmussen U, Håkonsson IH, Biering H, Rodien P, Tahara S, et al. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial. Eur J Endocrinol. 2018;178(5):491–9.