Endocrine Abstracts

JOINT1438

REAL 3 (NCT02616562) is a phase 2, randomised, multinational, open-label, active-controlled trial designed to determine treatment efficacy and safety of somapacitan, a long-acting growth hormone (GH) derivative, vs daily GH (Norditropin®, Novo Nordisk). Results after 4 years have been published (Sävendahl et al. JCEM 2023;108(10):2569-78). Here, we report final results at 7 years (364 weeks), representing the longest analysis of patients treated with somapacitan to date. Prepubertal children were recruited to three cohorts (I: GH-naïve, 2.5 to 9/10 years for girls/boys respectively; II: <2.5 years; III: 9/10 to 17 years for girls/boys, respectively). In cohort I, participants were randomised 1:1:1:1 to somapacitan (0.04 vs 0.08 vs 0.16 mg/kg/week) or daily GH 0.034 mg/kg/day. After 52 weeks, participants on somapacitan were all switched to the 0.16 mg/kg/week dose, while participants on daily GH continued unchanged. After 156 weeks, all participants, including those previously on daily GH, received somapacitan 0.16 mg/kg/week during a further 208-week long-term safety extension. Cohorts II and III only participated between weeks 156–364 and received somapacitan 0.16 mg/kg/week. In cohort I, 33 of 45 participants randomised to somapacitan (somapacitan-only group) and 10 of 14 participants randomised to daily GH (switch group) completed the long-term safety extension. Completion was similarly high in cohorts II (n=1/1) and III (n=11/16). Two participants in cohort I achieved near adult height by week 364. Efficacy results (mean [SD]) are reported for cohort I at week 364. Height velocity (HV) was 5.7 (2.2) cm/year in both groups and HV standard deviation scores (SDS) were 0.47 (1.13) and 0.57 (1.16) in the somapacitan-only and switch groups, respectively. Height SDS was −0.39 (1.15) in the somapacitan-only group and −0.54 (0.76) in the switch group. Year-on-year increases in height SDS were observed after week 156 in both groups. Insulin-like growth factor-I (IGF-I) SDS was 0.64 (1.68) and 0.79 (1.02) in the somapacitan-only and switch groups, respectively. Safety was assessed across all cohorts and no new safety signals were observed. Total patient-years of exposure to somapacitan 0.16 mg/kg/week was 327.4. After 7 years (364 weeks) of treatment, height SDS and IGF-I SDS were within the reference range (−2 to +2 SDS). Similar responses were observed in patients treated with somapacitan throughout the trial and in those who switched from daily GH after 156 weeks. No side effects for somapacitan outside the known safety profile of daily GH were identified.