Abstract 102

Abstract

Treatment of short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that can be burdensome for patients and caregivers. Once-weekly somapacitan is a long-acting GH in phase 3 development for replacement therapy in children with GH deficiency. We report the 52-week results of the first phase 2, multinational, randomised, open-label, controlled, dose-finding trial (NCT03878446) investigating efficacy and safety of somapacitan as treatment for short stature in children born SGA compared with daily GH (Norditropin®, Novo Nordisk A/S). Sixty-two (62; 35.5% female) GH-treatment-naïve, prepubertal children received 0.16, 0.20 or 0.24 mg/kg/week subcutaneous (s.c.) somapacitan, or 0.035 or 0.067 mg/kg/day s.c. GH. All children were subsequently included in a long-term safety extension trial. At week 52, the observed mean height velocity (HV) was 8.5, 10.3 and 10.6 cm/year for 0.16 (n = 12), 0.20 (n = 13) and 0.24 mg/kg/week (n = 12) somapacitan, respectively, versus 9.4 and 11.2 cm/year for 0.035 (n = 11) and 0.067 mg/kg/day (n = 13) GH, respectively. The effect of the three somapacitan doses vs. GH on HV was not statistically significantly different. A similar pattern as seen for HV was observed for changes from baseline in height standard deviation score (SDS) and HV SDS. Dose-dependent increases in IGF-I SDS were observed with somapacitan and GH, and significant exposure-response relationships to HV were established for somapacitan. Among the somapacitan doses investigated, 0.24 mg/kg/week provided an IGF-I response most similar to that of 0.067 mg/kg/day GH. All somapacitan doses were well tolerated; no safety concerns were identified. Reported AEs were mild to moderate; most were evaluated as unlikely related to treatment by the investigator. The tolerability profile was favourable and consistent with that of GH. Low-titre non-neutralizing hGH anti-drug antibodies were detected in one child in the GH 0.067 mg/kg/day arm; none were detected in other treatment arms. One patient treated with somapacitan 0.20 mg/kg/week developed type 1 diabetes mellitus. This event was evaluated as not related to the treatment. Otherwise, there were no clinically relevant findings with respect to glucose metabolism. In conclusion, these data support that 0.24 mg/kg/week somapacitan appears most efficacious of the somapacitan doses investigated in short children born SGA after 52 weeks of treatment. Furthermore, the safety and tolerability profiles of this dose are similar to those of 0.067 mg/kg/day GH.