017–Safety and Efficacy of Somavaratan (VRS-317), a Long-Acting Growth Hormone, in Children with Growth Hormone Deficiency (GHD): 2.5-Year Results from the VISTA Trial

Abstract

Background: Recombinant human growth hormone (rhGH) is the mainstay of treatment for children with GHD, but requirement for daily subcutaneous injections represents a treatment burden for patients and caregivers. Somavaratan is a novel, long-acting rhGH fusion protein with an extended half-life that allows less frequent dosing than daily rhGH. Somavaratan previously showed clinically meaningful improvements in height velocity (HV) and insulin-like growth factor (IGF)-I in children with GHD (VISTA Trial; NCT01718041). Aims: To evaluate somavaratan in pre-pubertal children with GHD after 2.5 years of treatment in an ongoing, long-term safety study. Methods: Pediatric doses established in a single dose PK/PD study (n=48) were tested for 6 months at weekly, twice-monthly, and monthly schedules (total 5.0 mg/kg/month; n=64). Sixty patients entered the long-term safety study. All transitioned to the 3.5 mg/kg twice-monthly regimen by beginning of the second year, based on growth and IGF-I responses during the first 6-12 months of treatment. Results: 24 girls and 33 boys with mean baseline age of 7.8 years were evaluable. Mean IGF-I SDS was 1.49 at screening vs. 0.59 at peak (3-5 days post injection) and 0.47 at trough (end of dosing cycle) during Year 2. IGF-I SDS excursions >2.0 occurred in 8 patients receiving the 3.5 mg/kg twice-monthly dose, of which 2 were >3.0. Increasing dose to 3.5 mg/kg twice-monthly resulted in similar HV between Years 1 and 2 (8.08 and 7.83 cm/year, respectively) and continued improvement in height-SDS (-2.6 [baseline] vs. -2.1 and -1.6, respectively). Mean increases in bone age and height age exceeded years on study. Differences between chronological age and bone age decreased over time. Treatment-related adverse events (AE) were generally mild and transient, with rates decreasing over time and no safety signals reported. Conclusions: Somavaratan improved IGF-I and HV with declining AEs over 2.5 years in pre-pubertal children with GHD. The 3.5 mg/kg twice-monthly dose, currently under evaluation in an ongoing phase 3 trial (VELOCITY; NCT02339090), is supported by comparable US NCGS estimates of second year HV from daily rhGH. Clinical implications: Somavaratan may reduce the need for daily dosing of rhGH, thus enabling a lighter treatment burden without compromising safety or efficacy in children with GHD.