A Randomized Safety and Efficacy Study of Somavaratan (VRS-317), a Long-Acting rhGH, in Pediatric Growth Hormone Deficiency.

CONTEXT Somavaratan (VRS-317) is a long-acting form of recombinant human GH under development for children and adults with GH deficiency (GHD). OBJECTIVES To determine the optimal somavaratan dose regimen to normalize IGF-1 in pediatric GHD and to evaluate safety and efficacy of somavaratan over 6 months. DESIGN Open-label, multicenter, single ascending dose study followed by 6-month randomized comparison of 3 dosing regimens. SETTING Twenty-five United States pediatric endocrinology centers. PATIENTS Naive-to-treatment, prepubertal children with GHD (n = 68). INTERVENTION(S) Patients received single sc doses of somavaratan (0.8, 1.2, 1.8, 2.7, 4.0, or 6.0 mg/kg) during the 30-day dose-finding phase, then were randomized to somavaratan 1.15 mg/kg weekly, 2.5 mg/kg twice monthly, or 5.0 mg/kg monthly for 6 months. MAIN OUTCOME MEASURES Safety, pharmacokinetics, pharmacodynamics, 6-month height velocity (HV). RESULTS Somavaratan pharmacokinetics was linearly proportional to dose; dose-dependent increases in the magnitude and duration of IGF-1 responses enabled weekly, twice-monthly or monthly dosing. A single dose of somavaratan sustained IGF-1 responses for up to 1 month. No somavaratan or IGF-1 accumulation occurred with repeat dosing. Mean annualized HVs for somavaratan administered monthly, twice monthly, or weekly (7.86 ± 2.5, 8.61 ± 2.7, and 7.58 ± 2.5 cm/y, respectively) were similar between groups. Adverse events were mostly mild and transient. CONCLUSIONS Somavaratan demonstrated clinically meaningful improvements in HV and IGF-1 in prepubertal children with GHD, with no significant differences between monthly, twice-monthly, or weekly dosing.