ESPE Abstracts

Growth hormone (GH) replacement therapy currently requires daily subcutaneous injections. Somapacitan is a long-acting GH-derivative in development for once-weekly use in children with GH deficiency (GHD). A phase 2, multinational, randomised, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n = 16), 0.08 (n = 15) or 0.16 mg/kg/week (n = 14) somapacitan, or daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n = 14) for 1 year, followed by a 2-year safety extension with all patients on somapacitan (n = 45) receiving 0.16 mg/kg/week, while daily GH dose was unaltered. Safety endpoints comprised frequency of adverse events (AEs). The 1-year and 2-year results have been reported previously. Here, we report the efficacy and safety of somapacitan after 3 years of treatment. At year 3, mean (SD) height velocity (HV) was 8.9 (1.7), 7.8 (1.5) and 8.4 (1.7) cm/year for 0.04/0.16 mg/kg/week, 0.08/0.16 mg/kg/week and 0.16/0.16 mg/kg/week somapacitan, respectively, vs 7.6 (2.0) cm/year for daily GH. Change in mean (SD) height standard deviation score (SDS) from baseline to 3 years was 2.39 (1.00), 2.37 (0.97) and 2.67 (1.42) for somapacitan, respectively, vs 2.10 (0.85) for daily GH. The observed HV results for the somapacitan groups and daily GH arm in the third year, were similar. Change in insulin-like growth factor-I SDS from baseline to year 3 was 3.26 (1.04), 3.52 (1.43) and 3.66 (1.29) for somapacitan, respectively, vs 3.40 (1.58) for daily GH. Number of AEs (% of patients) was as follows: somapacitan 0.04/0.16 mg/kg/week, 72 (75.0%); 0.08/0.16 mg/kg/week, 126 (93.3%); 0.16/0.16 mg/kg/week, 120 (100%); and daily GH, 95 (100%). In all treatment groups, the rate of AEs per 100 patient-years of exposure was lower in the 2-year safety extension than the first year. The most common AEs across the pooled somapacitan groups were pyrexia (40% for somapacitan and 14% for daily GH), influenza (20% and 21%), nasopharyngitis (16% and 21%), vomiting (13% and 7%), constipation (11% and 0%), allergic rhinitis (11% and 21%), otitis media (11% and 7%), tonsillitis (11% and 0%) and gastroenteritis (11% and 14%). Most AEs were mild to moderate and unlikely to be treatment related. These 3-year data support the efficacy results observed in the first and second year of somapacitan treatment of GHD; no new safety signals were observed.