Real-World Safety and Effectiveness of Vosoritide in Achondroplasia: Results from a Single Center in Portugal.

introductionAchondroplasia, the most common skeletal dysplasia, is caused by autosomal dominant gain-of-function pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Vosoritide, a C-type natriuretic peptide analog, is a first-in-class targeted treatment for achondroplasia that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth. This retrospective cohort study evaluated growth, safety, and treatment compliance in children with achondroplasia receiving vosoritide under an early access program in Portugal.

methodsTwenty-seven children aged 2-14 years with a genetically confirmed diagnosis of achondroplasia were treated with vosoritide at a single Portuguese center for at least 6 months between January 2022 and June 2024. The analysis included children with severe achondroplasia-associated complications. Anthropometric measurements collected to characterize the effect of vosoritide on growth included height standard deviation score (SDS) and annualized growth velocity (AGV). Student's t test was used for statistical comparisons. Safety and tolerability endpoints included adverse drug reactions and treatment adherence.

resultsIn total, 15 children completed at least 24 months of treatment. After 24 months of treatment, mean variation in height SDS increased from baseline by + 0.95 SD (P ≤ 0.0001), referenced to an untreated achondroplasia-specific population, and + 0.56 SD (P ≤ 0.0001) relative to children of average stature. Additionally, mean AGV from baseline was 5.87 cm/year (95% confidence interval 5.14-6.60), resulting in a significant increase of + 1.62 cm/year (P ≤ 0.0001). Injection site reactions were the most common adverse drug reaction observed (n = 14); no serious adverse drug reactions were reported. There were no discontinuations due to adverse drug reactions.

conclusionVosoritide showed long-term effectiveness in a real-world Portuguese population of patients with achondroplasia. Vosoritide was also well tolerated, and patients showed good adherence to treatment. These findings were consistent with the outcomes of clinical trials and existing real-world experience.