Background: Growth hormone deficiency (GHD) requires long-term daily injections with GH replacement therapy and is associated with considerable treatment burden by patients and caregivers. Somapacitan is a long-acting GH derivative that is being developed for once-weekly dosing in adults and children with GHD. A well-established protraction method, which is successfully in use to extend the half-life of insulin and glucagon-like peptide (GLP)-1, has been applied in developing somapacitan: an albumin-binding moiety (1.3 kDa) has been attached to a single point mutation in the amino acid backbone of the GH molecule (22 kDa).
Objective: To evaluate the safety, tolerability and efficacy of three different once-weekly somapacitan doses, compared with Norditropin, a daily GH.
Design: A multicentre, open-label, randomised, controlled phase 2 trial in children with GHD (ClinicalTrials.gov: NCT02616562; REAL 3). The trial was double-blinded with regard to dose levels of somapacitan, and height measurements were performed by assessors blinded to treatment allocation.
Methods: Fifty-nine GH-treatment-naïve prepubertal children with GHD were randomised to either somapacitan (N=45) or Norditropin (N=14). Subjects received one of three subcutaneous (s.c.) somapacitan doses: 0.04 (n=16), 0.08 (n=15), or 0.16 mg/kg per week (n=14) administered once-weekly, or s.c. Norditropin 0.034 mg/kg per day (0.24 mg/kg per week; n=14). Fifty-six patients completed 6 months of treatment, as follows: n=14, 15 and 14 in the somapacitan 0.04, 0.08 and 0.16 mg/kg/wk groups, respectively, and n=13 in the Norditropin group.
Results: Mean (S.D.) annualised height velocity (HV) for the three somapacitan doses was 8.0 (2.0), 10.9 (1.9) and 12.9 (3.5) cm, respectively. For the 0.08 and 0.16 mg/kg per week doses, HV did not differ statistically significantly from HV with Norditropin (11.4 [3.3] cm). Insulin-like growth factor (IGF)-I and IGF-binding peptide 3 (IGFBP-3) showed a dose-dependent increase during somapacitan treatment. Somapacitan was well tolerated at all doses investigated, with no clinically relevant safety or local tolerability issues identified. Adverse events were mild to moderate; most were evaluated as unrelated to the trial drug by the investigator; and tolerability was consistent with known properties of GH.
Conclusions: This phase 2 trial confirms the long-acting mechanism of somapacitan. Efficacy, safety and tolerability were similar to those of Norditropin in children with GHD. These data provide support for initiation of a phase 3 trial, using once-weekly injections of somapacitan, in children with GHD.
27 Sep 2018 - 29 Sep 2018