Background: Somavaratan, a novel long-acting rhGH fusion protein with t1/2>100 h, previously demonstrated clinically meaningful improvements in height velocity (HV) and IGF-I in prepubertal GHD children (Moore JCEM 2016).
Objective and hypotheses: To evaluate maintenance of somavaratan treatment effects in the 2nd treatment year.
Method: After subcutaneous pediatric doses were evaluated in a single dose PK/PD study (n=48), 64 subjects were randomized to weekly, twice-monthly (TM) and monthly dosing groups for total dose of 5.0 mg/kg per month for 6 months. Sixty subjects entered an extension study. Somavaratan dosing was adjusted to 3.5 mg/kg TM by start of Year 2, based on growth and IGF-I responses from the first 612 months of treatment.
Results: A total of 24 females and 33 males were evaluable in Year 2 (mean age, 7.8 years). Baseline HT-SDS was −2.6±0.6, IGF-I SDS −1.5±0.8, and GHmax 5.3±2.6 ng/mL. During Year 2, IGF-I SDS was 0.65±1.2 at peak (35 days postinjection) and −0.45±1.1 at trough (end of dosing cycle); 8 subjects had peak IGF-I SDS >2.0, of which two were >3.0 (range, 2.013.67). From Years 1 to 2, mean HV was maintained (8.1±2.2 vs 7.8±2.3 cm/year), and HT-SDS showed continued improvement (−2.1±0.6 vs −1.6±0.7). Over two years, mean bone age (BA) advanced by 2.4 years, mean height age by 2.7 years. Differences between chronological age and BA (years) were 1.5±0.8 at screening, 1.4±0.9 at Year 1, and 1.0±1.0 at Year 2. Related AE rates declined in Year 2 (n=7). Related AEs were generally mild and transient, with no new types reported.
Conclusion: Somavaratan in prepubertal children with GHD improved IGF-I and HV through 2 years, with AE rates declining over time. The 3.5 mg/kg TM dose maintained HV at levels similar to second-year US NCGS data for daily rhGH, and is being evaluated in a Phase 3 study in treatment-naïve GHD children (NCT02339090).
10 - 12 Sep 2016
European Society for Paediatric Endocrinology