Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial.

Context: Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in children with GH deficiency (GHD).

Objective: To demonstrate efficacy and safety of somapacitan vs daily GH.

Methods: REAL4 is a randomised, multinational, open-labeled, active-controlled parallel group phase 3 trial, comprising a 52-week main trial and 3-year extension (NCT03811535).

Setting: Eighty-six sites across 20 countries.

Patients: 200 treatment-naïve patients were randomized and exposed.

Interventions: Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (Norditropin; 0.034 mg/kg/d), administered subcutaneously.

Main Outcome Measures: The primary endpoint was annualized height velocity (HV; cm/y) at week 52. Additional assessments included HV SD score (SDS), height SDS, bone age, IGF-I SDS, patient-reported outcomes, and safety measures.

Results: Estimated mean HV at week 52 was 11.2 and 11.7 cm/y for somapacitan and daily GH, respectively. Noninferiority was confirmed. Changes in HV SDS, height SDS, bone age, and IGF-I SDS from baseline to week 52 were similar between treatment groups. At week 52, mean IGF-I SDS values were similar between treatment groups and within normal range (-2 to +2). Safety of somapacitan was consistent with the well-known daily GH profile. Low proportions of injection-site reactions were reported for somapacitan (5.3%) and daily GH (5.9%). Both treatments similarly reduced disease burden from baseline to week 52, whereas a greater treatment burden reduction was observed for somapacitan.

Conclusions: Similar efficacy for somapacitan compared to daily GH was demonstrated over 52 weeks of treatment with comparable safety and mean IGF-I SDS levels in treatment-naïve children with GHD.