Real-world safety and age-dependent effectiveness of vosoritide in achondroplasia: A single-center retrospective analysis of transition from growth hormone to vosoritide

Achondroplasia (ACH), a skeletal dysplasia, is characterized by disproportionate short stature and impaired quality of life. In Japan, growth hormone (GH) therapy has been available since 1997, and vosoritide, a C-type natriuretic peptide analog, was approved in 2022. Although clinical trials have demonstrated vosoritide's efficacy, real-world comparative data in Japan are scarce. We conducted a retrospective study of 22 children with ACH treated with vosoritide for over 6 months at a single institution between February 2018 and May 2025. Patients were divided into two groups: GH-naïve group (Group A, n = 13), receiving vosoritide alone, and a switch group (Group B, n = 9), who transitioned from prior GH treatment. Growth outcomes included annualized growth velocity (AGV) and height standard deviation scores (HT-SDS) calculated using Japanese and ACH-specific (HT-SDS_ACH) references. Group A (median age: 2.10 years) demonstrated significant improvements in HT-SDS_ACH at years 3 (p = 0.0022), 4 (p = 0.0004), 5 (p = 0.007), and 6 (p = 0.0012). Group B (median age: 10.1 years), with a median of 6.10 years of GH exposure, showed significant increases at 1 year (p = 0.047) and 2.5 years (p = 0.0054) after switching. In Group B, HT-SDS_ACH remained stable among patients starting vosoritide before age 4, but improved significantly in those beginning later. Injection site pain occurred in three patients, leading to one discontinuation. Vosoritide improves linear growth in children with ACH, including those previously treated with GH, showing greater benefit when started at ≥4 years, though earlier use may offer advantages.