A Phase 3 Trial of Vosoritide in Children with Hypochondroplasia.
Vosoritide significantly increased growth velocity in children with hypochondroplasia compared to placebo 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 annualized 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
<h4>Background</h4>Hypochondroplasia, a fibroblast growth factor receptor 3 (<i>FGFR3</i>)-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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>One year of vosoritide treatment significantly increased linear growth in children with hypochondroplasia. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT06455059.).
Background
Hypochondroplasia is a condition linked to mutations in the FGFR3 gene, resulting in disproportionate short stature. Prior to this study, there were no targeted therapies available for this condition. Vosoritide, a C-type natriuretic peptide analogue, has shown promise in treating achondroplasia and is being investigated for its effects on hypochondroplasia.
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 a duration of 52 weeks. The primary endpoint was the change from baseline in annualized growth velocity at week 52.
Results
At week 52, the LSM 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 a two-sided P-value of less than 0.0001.
Interpretation
The results indicate a statistically significant increase in growth velocity with vosoritide compared to placebo. However, while the effect size is statistically significant, its clinical significance may require further evaluation in larger populations. The study's small sample size and industry funding could limit the generalizability of the findings.
Key findings
- At week 52, 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.
- 87.8% of participants in the vosoritide group experienced at least one adverse event.
- 72.5% of participants in the placebo group experienced at least one adverse event.
- No reports of grade 3 or higher AEs, AEs leading to treatment discontinuation, or deaths.
Limitations
- small n=81 participants
- industry-funded by BioMarin Pharmaceutical
- short follow-up of 52 weeks
- no reports of grade 3 or higher adverse events