ESPE Abstracts

Somapacitan (Novo Nordisk A/S) is a long-acting GH derivative, approved for once-weekly administration in children and adults with GHD. IGF-I is monitored and includes a fraction bound to binding proteins, e.g., IGF binding protein-3 (IGFBP-3). The IGF-I/IGFBP-3 molar ratio can be used as surrogate marker for freely circulating bioactive IGF-I. REAL4 is a randomised, open-label, multi-national phase 3 trial (NCT03811535) with a 52-week main phase and a 3-year extension (week 52-208). The trial randomised (2:1) 200 GH-treatment-naïve, prepubertal children with GHD to once-weekly somapacitan (0.16 mg/kg; n = 132) or once-daily GH (Norditropin^® 0.034 mg/kg; n = 68) for 52 weeks. Subsequently, participants on daily GH switched to once-weekly somapacitan (switch group), while those on somapacitan continued treatment (soma/soma group). IGF-I SDS was the main pharmacodynamic endpoint. Blood samples were collected at week 0, 4, 13, 26, 39, 52, 78, 104, 130, and 156. For somapacitan, sampling was intended on day 1-4 after dosing (around peak; week 4, 26, 78, 130), day 7 (around trough; week 13, 39, 104, 156), and day 4-6 (around average; week 52). Weekly average IGF-I SDS was estimated from pharmacokinetic/pharmacodynamic modelling. Other pharmacodynamic endpoints included IGFBP-3 SDS, and IGF-I/IGFBP-3 molar ratio. The 3-year pharmacodynamic results are presented here. In total, 188 participants (125 and 63 in the soma/soma and switch group, respectively) completed three years of treatment. Baseline mean (SD) IGF-I SDS was -2.03 (0.97) in the soma/soma group and -2.33 (1.03) in the switch group. At week 156, mean change (SD) IGF-I SDS from baseline was 1.79 (1.12) and 1.96 (1.02), respectively, with mean weekly average within normal range (-2.0 to +2.0). Mean change (SD) IGFBP-3 SDS at week 156 was 1.56 (0.96) in the soma/soma group and 1.53 (0.86) in the switch group, with mean values within normal range, and mean (SD) IGF-I/IGFBP-3 molar ratios were 19.35% (6.70) and 19.80% (7.97), respectively. During weeks 104-156, IGF-I SDS >2.0 was measured in 24 (19.1%) and 8 (12.3%) in the soma/soma and switch group. IGF-I SDS >2.0 at two consecutive visits occurred in 2 (1.7%) and 1 (1.7%), respectively, with no observed trend in the amount or type of AEs. In conclusion, after three years of somapacitan and two years of somapacitan following switch from daily GH, IGF-I SDS, IGFBP-3 SDS, and IGF-I/IGFBP-3 molar ratio were similar between groups, and mean IGF-I SDS and IGFBP-3 SDS were within normal range.