Effective GH Replacement With Once-weekly Somapacitan vs Daily GH in Children with GHD: 3-year Results From REAL 3

Abstract

Context: Current GH therapy requires daily injections, which can be burdensome. Somapacitan is a long-acting GH derivative in development for treatment of GH deficiency (GHD).

Objective: Evaluate the efficacy, safety, and tolerability of once-weekly somapacitan after 3 years of treatment.

Design: A multicenter, randomized, controlled, phase 2 study comparing somapacitan and once-daily GH for 156 weeks (NCT02616562).

Setting: Twenty-nine sites in 11 countries.

Patients: Fifty-nine children with GHD randomized (1:1:1:1) and exposed to treatment. Fifty-three children completed the 3-year period.

Interventions: Patients received somapacitan (0.04 [n = 14], 0.08 [n = 15], or 0.16 [n = 14] mg/kg/wk) or daily GH (n = 14) (0.034 mg/kg/d, equivalent to 0.238 mg/kg/wk) subcutaneously during the first year, after which all patients on somapacitan received 0.16 mg/kg/wk.

Main outcome measures: Height velocity (HV) at year 3; changes from baseline in height SD score (HSDS), HVSDS, and IGF-I SDS.

Results: The estimated treatment difference (95% CI) in HV for somapacitan 0.16/0.16 mg/kg/wk vs daily GH at year 3 was 0.8 cm/y (-0.4 to 2.1). Change in HVSDS from baseline to year 3 was comparable between somapacitan 0.16/0.16 mg/kg/wk, the pooled somapacitan groups, and daily GH. A gradual increase in HSDS from baseline was observed for all groups. At year 3, mean HSDS was similar for the pooled somapacitan groups and daily GH. Change from baseline to year 3 in mean IGF-I SDS was similar across treatments.

Conclusions: Once-weekly somapacitan in children with GHD showed sustained efficacy over 3 years in all assessed height-based outcomes with similar safety and tolerability to daily GH. A plain language summary (1) is available for this study.

Clinical trial information: This study has been registered at ClinicalTrials.gov, number NCT02616562 (REAL 3).

Keywords: childhood growth hormone deficiency; growth hormone; growth hormone deficiency; growth hormone replacement therapy; long-acting growth hormone; somapacitan.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.

Patient disposition. All patients treated with somapacitan switched to 0.16 mg/kg/wk dose after year 1. The FAS included randomly assigned children who received at least 1 dose of treatment. The SAS included all randomly assigned children who received at least 1 dose of randomized treatment. FAS, full analysis set; GHD, GH deficiency; SAS, safety analysis set.

Figure 2.

Height velocity (cm/year) by treatment group and by year. Data are observed mean (SD), FAS. All patients treated with somapacitan switched to 0.16 mg/kg/wk dose after year 1, as represented by the dashed bars at years 2 and 3 for the 0.04 and 0.08 mg/kg/wk somapacitan doses. Data for the pooled somapacitan groups are therefore not shown at year 1, indicated by N/A. FAS, full analysis set; HV, height velocity; N/A, not applicable.

Figure 3.

Height velocity SDS by treatment group and by year. Data are mean (SD), FAS. All patients treated with somapacitan switched to 0.16 mg/kg/wk dose after year 1, as represented by the dashed bars at years 2 and 3 for the 0.04 and 0.08 mg/kg/wk somapacitan doses. Data for the pooled somapacitan groups are therefore not shown at year 1, indicated by N/A. FAS, full analysis set; HVSDS, height velocity SD score; N/A, not applicable; SDS, SD score.

Figure 4.

Height SDS by treatment group and by year. Data are mean (SD), FAS. All patients treated with somapacitan switched to 0.16 mg/kg/wk dose after year 1, as represented by the dashed bars at years 2 and 3 for the 0.04 and 0.08 mg/kg/wk somapacitan doses. Data for the pooled somapacitan groups are therefore not shown at year 1, indicated by N/A. FAS, full analysis set; N/A, not applicable; SDS, SD score.

Figure 5.

Mean IGF-I SDS: observed and derived values (FAS). Somapacitan trough values are an average from values obtained at week 143. Somapacitan peak values are an average from values obtained at week 156. Somapacitan average values were derived by population PK/PD modelling. Points and bars are means with SD. FAS, full analysis set; PK/PD, pharmacokinetic/pharmacodynamic; SDS, SD score.

Figure 6.

Bone age compared with chronological age per year. Data are mean (SD), FAS. FAS, full analysis set.

Figure 7.

Observer-reported outcomes: estimated treatment differences in change from baseline to years 1 and 3 between somapacitan and daily GH in treatment impact (GHD-CIM ObsRO) domain scores and total score (FAS). X marks represent minimal important differences. FAS, full analysis set; GHD-CIM ObsRO, Growth Hormone Deficiency–Child Impact Measure observer report.

Figure 8.

Most common adverse events, occurring in 10% or more of patients in any patient group. Safety analysis set. % indicates percentage of patients in each treatment group. R, event rate per 100 patient-years at risk.