Once-Weekly Somapacitan vs Daily GH in Children with GH Deficiency: The Randomized Phase 3 REAL 4 Trial
Background: Growth hormone (GH) replacement therapy usually requires daily subcutaneous (s.c.) injections that can be burdensome for patients and their caregivers. Long-acting GH formulations aim to establish a less burdensome dosing regimen that is as safe and efficacious as daily GH to potentially improve adherence and clinical outcomes. Somapacitan, a long-acting reversible albumin-binding GH derivative, is in development for once-weekly s.c. administration in children with GH deficiency (GHD). Design and Patients: REAL4 is a randomised, multi-national, open labelled, and active-controlled parallel group phase 3 trial (NCT03811535) investigating efficacy and safety of once-weekly somapacitan compared with daily GH (Norditropin®, Novo Nordisk). The trial comprises a 52-week main phase and 3-year safety extension. Two-hundred GH-treatment-naïve, prepubertal children with GHD (74.5% male) were enrolled and randomly assigned in a 2:1 ratio to receive 0.16 mg/kg/week s.c. somapacitan (n=132) or daily s.c. GH (0.034 mg/kg/day Norditropin®; n=68) for 52 weeks. Data presented here include secondary efficacy endpoints, including change from baseline to week 52 in height velocity standard deviation score (HVSDS), height SDS (HSDS), and bone age, as well as patient-reported outcomes (PROs) to assess disease and treatment burden.
Results: Non-inferiority in height velocity (cm/year) at week 52 was confirmed. Estimated changes in HVSDS and HSDS from baseline to week 52 were similar between once-weekly somapacitan (8.05 and 1.25, respectively) and daily GH (8.82 and 1.30, respectively) treatment groups, with no statistically significant differences. The mean estimated bone age to chronological age ratio advanced slightly and similarly in both groups (0.06 for somapacitan vs. 0.08 for daily GH), with no changes in skeletal proportions reported. PRO results demonstrate a similar reduction in disease burden between treatment groups from baseline to week 52. Treatment burden assessments at week 52 favour somapacitan over daily GH across all domains. The same high proportion of respondents (96%) found the somapacitan and Norditropin® FlexPro® devices to be easy or very easy to use, while a similarly high proportion of respondents (>90%) found the devices easy or very easy to learn to use. Safety was consistent with the daily GH profile.
Conclusions: The efficacy and safety profile of somapacitan was similar to the efficacy and safety profile of daily GH. Data from PRO questionnaires show that both treatments reduced the disease burden to a similar degree, while reduced treatment burden consistently favoured somapacitan over daily GH.
15 Sep 2022 - 17 Sep 2022