Effect of Vosoritide therapy on IGF-I and Endogenous C-type Natriuretic Peptide in Hypochondroplasia

Document Type

Journal Article

Publication Date

10-29-2025

Journal

The Journal of clinical endocrinology and metabolism

DOI

10.1210/clinem/dgaf591

Keywords

C-type natriuretic peptide; Hypochondroplasia; IGF-1; NTproCNP; vosoritide

Abstract

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 analog, increases annualized growth velocity (AGV) and height standard deviation (SD) in pre-pubertal 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 II clinical trial of vosoritide in pre-pubertal patients ages 3-11y with HCH and height <-2.25 SD. Subjects were followed for a baseline 6-month observation period and then received a dose of 15μg/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 (Rho=0.57, p=0.024). CONCLUSIONS: 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.

Department

Pediatrics

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