A Phase 3 Trial of Vosoritide in Children with Hypochondroplasia.
Vosoritide treatment resulted in a significant increase in growth velocity in children with hypochondroplasia over one year, but further studies are needed to confirm these findings.
Where it sits
this study against the rest of the vosoritide corpusSummary and findings
This study measured the effect of vosoritide on growth velocity in children with hypochondroplasia over 52 weeks. A total of 81 participants were randomly assigned to receive either vosoritide or placebo. The results indicated a significant increase in growth velocity with vosoritide compared to placebo.
Abstract
Background Hypochondroplasia, a fibroblast growth factor receptor 3 (FGFR3)-related skeletal condition characterized by disproportionate short stature and a spectrum of clinical features, has no available targeted therapies. Vosoritide, a C-type natriuretic peptide analogue approved for the treatment of achondroplasia, is being investigated for hypochondroplasia. Methods In this phase 3, multicenter trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen. The primary end point was change from baseline in annualized growth velocity at week 52 versus placebo. Confirmatory statistical testing using hierarchical procedures to control for type I error at the one-sided 0.025 significance level (equivalent to the two-sided 0.05 level) was performed for the primary and six key secondary efficacy end points. The safety and side effect profile of vosoritide versus placebo was assessed. Results A total of 81 participants were randomly assigned to receive vosoritide (n=41) or placebo (n=40). At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus -0.39 cm/year with placebo (LSM difference of 2.33 cm/year; 95% confidence interval, 1.85-2.82 cm/year; two-sided P<0.0001). Most participants in the vosoritide group (87.8%) and the placebo group (72.5%) experienced at least one adverse event (AE). There were no reports of grade 3 or higher AEs, AEs leading to treatment discontinuation, or deaths. Conclusions One year of vosoritide treatment significantly increased linear growth in children with hypochondroplasia. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT06455059.).
Background
This paper addresses the treatment of hypochondroplasia, a condition associated with short stature due to mutations in the FGFR3 gene. Prior to this study, there were no targeted therapies available for this condition. The investigation of vosoritide, a C-type natriuretic peptide analogue, is significant as it aims to provide a potential treatment option.
Methods
This phase 3, multicenter trial involved children aged 3 to less than 18 years with hypochondroplasia. Participants were randomly assigned to receive either vosoritide or placebo via once-daily subcutaneous injections for 52 weeks. The primary outcome measure was the change from baseline in annualized growth velocity at week 52.
Results
At week 52, the least squares mean change from baseline in annualized growth velocity was 1.95 cm/year for the vosoritide group compared to -0.39 cm/year for the placebo group. The LSM difference was 2.33 cm/year with a 95% confidence interval of 1.85-2.82 cm/year, and the result was statistically significant with a two-sided P-value of less than 0.0001.
Interpretation
The findings indicate a statistically significant increase in growth velocity with vosoritide compared to placebo, which may suggest a potential benefit for children with hypochondroplasia. However, the clinical significance of a 2.33 cm/year increase should be considered in the context of overall growth patterns and individual patient needs. Limitations such as the small sample size and potential industry funding bias may affect the robustness of these conclusions.
Key findings
- 1.95 cm/year change in annualized growth velocity with vosoritide at week 52, n=41.
- -0.39 cm/year change in annualized growth velocity with placebo at week 52, n=40.
- LSM difference of 2.33 cm/year between vosoritide and placebo, 95% CI 1.85-2.82 cm/year, two-sided P<0.0001.
- 87.8% of vosoritide group experienced at least one adverse event.
- 72.5% of placebo group experienced at least one adverse event.
Limitations
- small n=81 participants
- industry-funded by BioMarin Pharmaceutical
- short follow-up of 52 weeks
- no reports of long-term effects