ESPE Abstracts

Daily subcutaneous (s.c.) injections of growth hormone (GH) to treat GH deficiency (GHD) in children is burdensome for both patients and caregivers. Somapacitan (Novo Nordisk) is a long-acting reversible albumin-binding human GH derivative in development for once-weekly s.c. administration in children with GHD, and aims to overcome the treatment burden of daily injections. REAL4 is a multi-national, randomised, open labelled phase 3 trial with a 52-week main phase followed by a single-group three-year extension (NCT03811535). During the main phase, 132 patients received once-weekly 0.16 mg/kg/week somapacitan with another 68 receiving daily GH (0.034 mg/kg/day Norditropin®, Novo Nordisk). Following 52-weeks, patients receiving somapacitan continued treatment (soma/soma group) and patients receiving daily GH were switched to somapacitan (switch group). In year two, 194 patients (127 and 67 for soma/soma and switch groups, respectively) completed 104-weeks of treatment, with results presented here. Height velocity (HV) was similar between groups during the 2-year period with HV at week 104 being 8.7 vs. 8.4 cm/year for the switch and soma/soma groups, respectively. Other height-related assessments supported these findings. For example, a continuous increase in HSDS was observed with measurements for the switch and soma/soma groups being -3.47 and -2.99 at week 0, -2.09 and -1.78 at week 52, and -1.47 and -1.23 at week 104, respectively. IGF-I SDS increased in both groups (observed mean IGF-I SDS at week 104 was -0.25 and -0.27 for the switch and soma/soma groups, respectively) with mean IGF-I SDS within normal range (-2 to +2) during the study. PK/PD modelling suggests similar mean average IGF-I levels over the weekly dosing interval for both groups in year 2. Somapacitan was well tolerated, with no safety or local tolerability issues identified. A low number of patients reported injection-site reactions in the second year, with no injection-site pain reported. Patient preference questionnaires were responded to by 50 caregivers of patients in the switch group. Almost all (90%) preferred somapacitan with none preferring daily GH. The top reason given for this preference was the frequency of injections. Of the 45 caregivers who preferred somapacitan, 35 (77.8%) believed they would be more adherent to treatment with somapacitan rather than daily GH. In conclusion, once-weekly somapacitan, for 2 years, or for 1 year after switching from daily GH, was efficacious and well-tolerated. A preference for somapacitan was reported in those who switched from daily GH.