Abstract
Background: Achondroplasia is a disorder caused by specific mutations in the gene encoding the fibroblast growth factor receptor 3 (FGFR3) protein. Open-label, phase 2 trials in children with achondroplasia showed that administration of vosoritide, an analogue of C-natriuretic peptide, resulted in sustained increases in annualized growth velocity. Methods: This international, randomized, double-blind, phase 3 trial compared once-daily subcutaneous administration of vosoritide, at a dose of 15 μg per kg of body weight, with placebo in children with achondroplasia aged 5 to <18 years. Eligible patients had participated, for at least 6 months, in an observational growth study in order to calculate their baseline annualized growth velocity. The primary efficacy endpoint was the change from baseline in annualized growth velocity at week 52 of treatment. The primary analysis of the change from baseline in annualized growth velocity was performed using an ANCOVA model. Results: A total of 121 patients were randomized, with 60 assigned to receive vosoritide and 61 to receive placebo. A total of 119 patients completed the 52-week trial. The adjusted mean difference in annualized growth velocity between patients administered vosoritide and those administered placebo was 1.57 cm per year in favor of vosoritide (95% CI: [1.22, 1.93], two-sided p-value <0.001). A total of 119 patients experienced at least one adverse event (vosoritide group, 59 [98.3%], placebo group, 60 [98.4%]). Conclusions: Daily, subcutaneous administration of vosoritide to children with achondroplasia resulted in a significant increase in mean annualized growth velocity and similar incidence of adverse events compared to placebo.