Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4.

OBJECTIVE: Somapacitan is a long-acting GH approved for once-weekly treatment of GH deficiency (GHD). This study aims to evaluate the efficacy and tolerability of somapacitan after 3 years of treatment and 2 years after switch from daily GH in children with GHD. DESIGN: Randomized, multi-national, open-labelled, active-controlled parallel-group phase 3 trial, with a 52-week main phase and 3-year safety extension (NCT03811535). METHODS: Treatment-naïve children with GHD were randomized (2:1) to continuous somapacitan (0.16 mg/kg/week; "soma/soma" group) or daily GH (Norditropin®; 0.034 mg/kg/day) followed by somapacitan (0.16 mg/kg/week; "switch" group). RESULTS: Of 200 participants, 188 completed 3 years of treatment. Sustained growth was observed in both groups. At week 156, mean (SD) height velocity (HV) between weeks 104 and 156 was 7.4 (1.5) cm/year in the soma/soma group and 7.8 (1.4) cm/year in the switch group. At week 156, the soma/soma and switch groups had reached a mean (SD) height SD score (HSDS) of -0.95 (0.98) and -1.08 (0.93), respectively, and were approaching the mean mid-parental HSDS of -0.74 (for both groups). Mean total insulin-like growth factor I (IGF-I) SDS during year 3 was similar between groups and within normal range (-2.0 to +2.0). Bioactive IGF-I and bioactive IGF-I to IGF-I ratio were similar between groups. Somapacitan was well tolerated, with low proportions reporting injection-site reactions. CONCLUSIONS: Sustained efficacy and tolerability were observed for continuous somapacitan treatment for 3 years, and for 2 years after the switching from daily GH treatment. HSDS in both groups was approaching mean mid-parental HSDS. CLINICAL TRIAL REGISTRATION: NCT03811535.