Vosoritide daily injections in prepubertal hypochondroplasia patients over 12 months

CONTEXT: Insulin-like growth factor-1 (IGF-1) and C-type natriuretic peptide (CNP) promote endochondral bone growth. We previously reported that vosoritide, a CNP analogue, increases annualized growth velocity (AGV) and height SD in prepubertal children with hypochondroplasia (HCH). OBJECTIVE: We hypothesized that IGF-1 and CNP will be inversely associated at baseline and will respond differentially during a single-arm, unblinded, standardized 12-month phase 2 clinical trial of vosoritide in prepubertal patients aged 3 to 11 years with HCH and height less than -2.25 SD. Participants were followed for a baseline 6-month observation period and then received a dose of 15 μg/kg/day of vosoritide subcutaneous daily injections for 12 months. Anthropometrics, IGF-1, and NTproCNP were measured every 6 months. Longitudinal changes in IGF-1 and NTproCNP as well as the correlations between these 2 analytes and changes in height SD and AGV were analyzed. RESULTS: Baseline IGF-1 values are reduced in children with HCH and increased throughout the study, but IGF-1 SD did not change significantly. NTproCNP was raised at baseline and declined throughout the study, with NTproCNP SD significantly lower at months 6 and 12 on treatment. Change in height SD or AGV were not correlated to IGF-1 or NTproCNP SD at 12 months. The change in IGF-1 concentrations at 12 months was positively correlated with the change in NTproCNP plasma concentrations (ρ = 0.57; P = .024). CONCLUSION: In children with HCH, IGF-1 levels are reduced and NTproCNP levels are elevated at baseline. A correlation between changes in these levels during treatment suggests a possible interaction between IGF-1 and CNP signaling.