Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 4; pp. e1847 - e1861
• Main Authors: Sävendahl, Lars, Battelino, Tadej, Brod, Meryl, Højby Rasmussen, Michael, Horikawa, Reiko, Juul, Rasmus Vestergaard, Saenger, Paul
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.04.2020
• Subjects: Biomarkers - analysis; Child; Child, Preschool; Children; Double-Blind Method; Drug Administration Schedule; Dwarfism, Pituitary - drug therapy; Dwarfism, Pituitary - metabolism; Dwarfism, Pituitary - pathology; Female; Follow-Up Studies; Growth hormones; Human Growth Hormone - administration & dosage; Human Growth Hormone - classification; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3 - analysis; Insulin-like growth factor I; Insulin-Like Growth Factor I - analysis; Insulin-like growth factors; Male; Medicin och hälsovetenskap; Online Only; Physical growth; Prognosis; Safety; long-acting growth hormone; treatment burden; growth hormone replacement therapy; growth hormone; somapacitan; growth hormone deficiency
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgz310

Abstract Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).