Am J Med Genet A. 2026 Aug 31. doi: 10.1002/ajmg.a.70254. Online ahead of print.
ABSTRACT
Achondroplasia is a skeletal dysplasia associated with severe short stature and multisystem complications due to a gain-of-function pathogenic variant in the FGFR3 gene. Vosoritide, a C-type natriuretic peptide analog, has demonstrated efficacy in clinical trials. The objective of this study was to describe the effectiveness, safety, treatment continuity, and caregiver-reported outcomes of vosoritide in routine practice across heterogeneous health systems in Latin America in a real-world context. We conducted a retrospective, multicenter, multinational cohort study including children with molecularly confirmed achondroplasia treated with vosoritide in centers from Argentina, Colombia, Uruguay, Mexico, and Chile. Eligible patients had ≥ 6 months of treatment and at least two anthropometric evaluations. Height, annualized growth velocity (AGV), body proportion measures, treatment interruptions, adverse events, and parent-reported outcomes were analyzed. Fifty-two patients (mean age 5.9 years at treatment initiation) were included, with a mean treatment duration of 539 days and high adherence (93.9% time without interruptions). Height Z-scores increased significantly from 6 to 36 months (0.33 to 1.58; p < 0.001 to p < 0.05). The most significant impact in AVG is observed during the first year of treatment with vosoritide, followed by a subsequent stabilization, reaching growth rates comparable to those of the healthy population. Increases were consistent across sexes and age groups. All patients were in a higher percentile range for AGV during treatment compared to before treatment, in some cases exceeding the 95th percentile, when compared to reference curves. Body proportion indices remained stable. All patients demonstrated gains in linear growth, although the magnitude of increase varied across individuals. Adverse events were frequent but mild, mainly injection-site reactions; no severe adverse events or treatment discontinuations due to safety issues occurred. Parent-reported outcomes were highly favorable, with 98% of caregivers perceiving positive changes in their children's overall well-being, daily functioning, or quality of life, and all caregivers expressing willingness to recommend the treatment. In real-world clinical practice across Latin America, vosoritide demonstrated rapid and sustained gains in linear growth, favorable tolerability, high adherence, and meaningful benefits as perceived by caregivers. These results reinforce the generalizability of vosoritide therapy in heterogeneous healthcare systems and highlight the relevance of real-world evidence for informing treatment decisions in rare diseases.
PMID:42675811 | DOI:10.1002/ajmg.a.70254