Effect of Vosoritide Therapy on IGF-I and Endogenous C-Type Natriuretic Peptide in Hypochondroplasia
Clinical Snapshot
PICO Framework
| P — Population | Prepubertal children aged 3-11 years with hypochondroplasia and height <-2.25 SD |
| I — Intervention | Vosoritide 15 μg/kg/day subcutaneous daily injections for 12 months |
| C — Comparator | 6-month baseline observation period (within-subject comparison) |
| O — Outcomes | Changes in IGF-1 and NTproCNP levels, correlations with height SD and annualized growth velocity |
Bottom Line
This Phase 2 study provides mechanistic insights into vosoritide's effects on growth-related biomarkers in hypochondroplasia. Children showed reduced baseline IGF-1 and elevated NTproCNP levels, with treatment producing correlated changes in both markers. However, these biomarker changes did not correlate with actual growth improvements, limiting their utility as surrogate endpoints. The single-arm design and small sample size typical of rare disease studies limit causal inference. While biologically interesting, these findings primarily inform our understanding of CNP-IGF-1 pathway interactions rather than providing direct clinical guidance. Australian clinicians should note that vosoritide remains an investigational therapy not available through PBS, requiring careful consideration of access pathways for eligible patients with hypochondroplasia.
Key Findings
P Value: P = 0.024 for IGF-1/NTproCNP correlation
Effect Size: Positive correlation between IGF-1 and NTproCNP changes (ρ = 0.57)
Primary Outcome: Changes in IGF-1 and NTproCNP levels during vosoritide treatment
Nnt Or Sensitivity: Not applicable - biomarker correlation study
Confidence Interval: Not reported in abstract
Clinical Application
Limited by vosoritide availability and cost; requires specialized pediatric endocrinology expertise Vosoritide not currently PBS-listed; would require individual patient access schemes or private funding. Aligns with RACGP guidelines for specialist referral of growth disorders Australian children with hypochondroplasia meeting similar criteria (age 3-11 years, height <-2.25 SD)
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 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.
References
- 1.Kanakatti Shankar, R., Galetaki, D. M., Zhang, A., Shafaei, N., Pitner, K., Seaforth, R., Prickett, T., Espiner, E. A., & Dauber, A. (2026). Effect of Vosoritide Therapy on IGF-I and Endogenous C-Type Natriuretic Peptide in Hypochondroplasia. The Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgaf591
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