Daily injections are required for human growth hormone (GH) replacement therapy. Somapacitan is a long-acting GH derivative being developed for once-weekly dosing in adults and children using a proven protraction method, currently successfully in use to extend the half-life of insulin and glucagon-like peptide 1.
To evaluate the efficacy and safety of three different once-weekly somapacitan doses compared with Norditropin®, a daily GH, over 52 weeks in GH-treatment-naïve prepubertal children with GHD.
In this multicentre, open-label, randomised, controlled, double-blinded (with respect to dose), phase 2 study (ClinicalTrials.gov: NCT02616562), participants were randomised to somapacitan (n=45) or Norditropin® (n=14). Patients received 0.04 (n=16), 0.08 (n=15) or 0.16 (n=14) mg/kg/week subcutaneous somapacitan once weekly, or subcutaneous Norditropin® 0.034 mg/kg/day; n=14). Patients (n=56, 94.9%) completed 52 weeks of treatment: somapacitan 0.04 (n=14), 0.08 (n=15) and 0.16 (n=14) mg/kg/week, and Norditropin® 0.034 mg/kg/day (n=13).
At 52 weeks, mean (SD) annualised height velocity (HV, cm/year) for the three somapacitan doses was 7.8 (1.8), 9.7 (1.8) and 11.5 (2.6), respectively. HV for the 0.16 mg/kg/week dose was statistically significantly higher than for Norditropin® (10.0 [2.2])*. HV for the 0.08 mg/kg/week dose did not differ significantly from HV with Norditropin®. Mean (SD) change from baseline in HV standard deviation score (SDS) was 4.72 (2.79), 6.14 (3.36) and 8.60 (3.15) for the three somapacitan doses, respectively, and not significantly different from Norditropin® (7.41 [4.08]) for somapacitan 0.08 or 0.16 mg/kg/week. Derived mean (SD) insulin-like growth factor-I SDS for somapacitan 0.04, 0.08, and 0.16 mg/kg/week was -1.62 (0.86), -1.08 (0.81) and 0.41 (1.05), respectively, compared with -0.40 (1.50) observed for Norditropin®. Change in bone age appeared similar among all treatment groups. Adverse events (AEs) were generally mild to moderate in severity and most were considered unrelated to treatment. The rate of AEs for the highest dose of somapacitan (0.16 mg/kg/week) was the same as for Norditropin®. Five subjects had one single low-titre measurement of non-neutralising anti-somapacitan antibodies.
In children with GHD, the efficacy, safety and tolerability of once-weekly somapacitan were similar to those of daily GH, with the 0.16 mg/kg/week dose providing the closest overall efficacy match. These results provide support for the initiation of a phase 3 trial of somapacitan in children with GHD.
*Post-hoc defined analysis excluded one subject in the Norditropin® group, who prematurely discontinued treatment.
19 Sep 2019 - 21 Sep 2019