Once-Weekly Somapacitan vs Daily GH in Children With GH Deficiency: Results From a Randomized Phase 2 Trial

Abstract

Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once‐weekly somapacitan or daily growth hormone

“…The safety of somapacitan was further confirmed by results from the global phase 3 trial REAL 1, in which the overall safety and efficacy of somapacitan was found to be similar to daily GH in treatment‐naïve patients with AGHD 12 . In addition, somapacitan was found to have similar efficacy to daily GH in a phase 2 trial in children with GHD 13 . However, the efficacy in previously GH‐treated patients with AGHD switching from daily GH to once‐weekly somapacitan has not previously been investigated.…”

“…This may account for the slightly higher number of transient elevations in IGF‐I SDS to above +2 in the somapacitan‐treated patients. However, pharmacokinetic/pharmacodynamic modelling has shown that average IGF‐I levels over 1 week after dose titration are predicted to be similar between somapacitan and daily GH 13 . For the majority of patients in both treatment arms, IGF‐I SDS was below +2 for the duration of the trial.…”

Weekly Lonapegsomatropin in Treatment–Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial

“…The most easily measured indicator of the effectiveness of a GH therapy in children is linear growth; the evaluation of response during the first year (ie, catch-up growth) appears to be most important for prediction models calculating final height ( 21-23 ). In a Phase 2 study, mean AHV for the somapacitan 0.16 mg/kg/week group was 12.9 cm/year compared to 11.4 cm/year with daily somatropin 0.034 mg/kg/day at week 26 (not significantly different), with comparable safety ( 24 ). Somatrogon demonstrated noninferior AHV compared to daily somatropin (10.10 cm/year vs 9.78 cm/year) with a similar safety profile in a Phase 3 study ( 25 ).…”

Patient preferences for growth hormone treatment in Japanese children

“… 15 However, the frequency of preference for r‐hGH injection schedule in treating patients with GHD is not a clear concern, as currently only daily type is commercially available for treatment. 16 , 17 , 18 Patient preference research allows identification of the preferences for various treatment options and potential trade‐offs that participants are willing to make. 19 Patient preference for treatment is an essential dimension of health care that should be incorporated into decision making.…”