P4.A016: Weekly Somapacitan in Children with Growth Hormone Deficiency: Subgroup Analysis Results of the REAL4 Randomized Phase 3 Trial by Baseline Growth Hormone Peak Concentration

Background: This analysis aimed to determine differences between three groups of patients with growth hormone (GH) deficiency participating in REAL4, a randomized, multinational, open-labeled, active-controlled parallel group phase 3 trial (NCT03811535), stratified by peak GH concentration in GH-stimulation tests at diagnosis.

Methods: A total of 200 children with treatment-naïve prepubertal GH deficiency (GH peak ≤10.0 μg/L) aged ≥2.5 years were included in the trial at 85 sites across 20 countries. Patients were randomized 2:1 to receive somapacitan 0.16 mg/kg/week or GH 0.034 mg/kg/day during the first year, after which all patients received somapacitan 0.16 mg/kg/week. Outcome measures of height velocity (HV; cm/year), change in height standard deviation score (SDS) from baseline, and change in insulin-like growth factor-I (IGF-I) SDS from baseline were compared between treatment groups at weeks 52 and 104 for each of the three GH peak groups, defined post-hoc as: ≤3, >3 to < 7, and ≥7 to ≤10.0 μg/L at diagnosis.

Results: There were 61 patients with a GH peak concentration ≤3 μg/L at diagnosis and a mean (SD) age of 6.51 years (2.26) at baseline. Ninety-three patients had a GH peak of >3 to < 7 μg/L and a mean (SD) age of 6.01 years (2.23). Forty-six patients had a GH peak of ≥7μg/L; mean (SD) age was 7.02 years (2.34). Outcome variables for weeks 52 and 104 are shown in the Table. At week 52, for the daily GH and somapacitan treatment groups, estimated mean HV ranged from 14.1 to 12.8, 10.9 to 10.5, and 10.0 to 10.6 cm/year for the ≤3, >3 to < 7, and the ≥7μg/L GH peak groups, respectively. At week 104, for the daily GH/somapacitan and somapacitan/somapacitan groups, estimated mean HV ranged from 9.9 to 9.2, 8.1 to 8.0, and 8.0 to 7.9 cm/year, respectively for the aforementioned peak GH groups. Change in height SDS from baseline ranged from a mean of 1.89 to 1.59, 1.17 to 1.06, and 0.92 to 1.07 at week 52 and 2.79 to 2.30, 1.64 to 1.54, and 1.33 to 1.51 at week 104 for the ≤3, >3 to < 7, and the ≥7μg/L GH peak groups, respectively. The mean change in IGF-I SDS from baseline ranged from 3.13 to 3.01, 2.11 to 1.96, and 1.87 to 2.26 at week 52 and at week 104, the values ranged from 2.81 to 2.11, 1.85 to 1.62, and 1.28 to 1.71 for the three GH peak groups, respectively.

Conclusion: Compared to the >3 to < 7 and the ≥7μg/L GH peak groups at weeks 52 and 104 of the trial, patients with GHD in the ≤3μg/L GH peak group had increased HV and greater changes in height SDS and IGF-I SDS from baseline.