ESPE Abstracts

Somapacitan is currently the only long-acting GH approved by FDA, PDMA and EMA to treat GH deficiency (GHD) in both children and adults. Similar efficacy, safety, and tolerability in children with GHD was demonstrated for somapacitan (0.16 mg/kg/week) compared to daily GH (0.034 mg/kg/day) in the global phase 3 REAL4 study, which was conducted in 20 countries within Asia (excluding China), Europe, and North America. Efficacy and safety of somapacitan in Chinese children with GHD remains to be confirmed. REAL6 is a randomised, multi-site, open-labelled, and active-controlled parallel group phase 3 trial conducted in China (NCT04970654). Prepubertal, GH-treatment naïve Chinese children with GHD (n = 110; 86.4% male) were randomly assigned 2:1 to subcutaneously receive somapacitan (0.16 mg/kg/week; n = 74) or daily GH (0.034 mg/kg/day; n = 36) for 52-week weeks. In total, 103 completed 52 weeks of treatment. The primary endpoint was annualized height velocity (HV; cm/year) after 52 weeks of treatment. At week 52, estimated mean HV was 11.0 cm/year for somapacitan compared to 10.4 cm/year for daily GH. The estimated treatment difference was +0.6 cm/year [95%CI: -0.2;1.3], confirming non-inferiority (threshold: 2.0 cm/year). Secondary growth-related endpoints, such as change from baseline to week 52 in HV standard deviation score (SDS), height SDS, and bone age were similar between treatment groups. Change from baseline to week 52 in IGF-I SDS were observed for somapacitan and daily GH. At week 52, mean IGF-I SDS was within the intended reference range (-2.0 to +2.0) and was similar between somapacitan and daily GH groups (+0.5 and +0.1, respectively). Somapacitan was well tolerated, with no new safety or local tolerability issues identified. Most adverse events (AEs) were mild, with no apparent differences between groups. There were no clinically relevant findings with respect to changes in glucose metabolism, and injection-site reactions were reported by a low number of patients (2.7% and 11.1% for the somapacitan and daily GH groups, respectively). There were no reports of injection-site pain. One AE of adenoidal hypertrophy exacerbation (non-serious/mild in severity/possibly related to trial product) in the somapacitan group led to premature discontinuation of trial product. In conclusion, once-weekly somapacitan (0.16 mg/kg/week) has a similar efficacy and safety profile as daily GH (0.034 mg/kg/day) and display a similar mean IGF-I SDS in treatment-naïve Chinese children with GHD. These results closely mirror findings for the efficacy and safety of somapacitan compared to daily GH observed during the global phase 3 REAL4 study.