Once-weekly somapacitan enhances linear growth in girls with Turner syndrome: a randomized controlled phase 3 study

CONTEXT: Daily GH injections promote growth in girls with Turner syndrome (TS), but treatment burden is considerable. OBJECTIVE: This study aims to evaluate 52-week efficacy and safety of once-weekly somapacitan, a long-acting GH, in girls with TS. DESIGN: REAL8 (NCT05330325) is a randomized, open-labelled, active-comparator, phase 3 basket study with a 52-week main phase and a 104-week extension. SETTING: The study was conducted at 49 clinics in 18 countries worldwide. PARTICIPANTS: In total, 105 treatment-naïve, prepubertal girls with TS (aged 2.5-10 years), were randomized and exposed. No participants discontinued trial product due to adverse events. INTERVENTIONS: Participants were assigned 2:1 to somapacitan, 0.24 mg/kg/week, or daily GH 0.050 mg/kg/day, administered subcutaneously. MAIN OUTCOME MEASURES: The primary endpoint was height velocity (HV; cm/year) at week 52. RESULTS: Non-inferiority for once-weekly somapacitan vs. daily GH for the primary endpoint, HV at week 52, was confirmed. At week 52, mean observed HV was 9.0 (1.6) vs. 9.5 (2.2) cm/year for somapacitan and daily GH, respectively (ETD = -0.8 [-1.57; -0.11]95%CI). IGF-I SD score (SDS) increased in both groups. At week 52, mean (SD) IGF-I SDS was +1.71 (1.38) vs. + 1.95 (1.11) for somapacitan and daily GH, respectively. Safety profiles were similar between groups. CONCLUSIONS: Once-weekly somapacitan showed non-inferiority and is comparable to daily GH after 52 weeks of treatment in enhancing linear growth while maintaining IGF-I concentrations within a similar range in treatment-naïve girls with TS. Similar safety profiles and tolerability were observed for both groups.