Real-World Evidence on the Effectiveness and Safety of Vosoritide in Latin American Patients With Achondroplasia (EVOLAC).
Vosoritide treatment in children with achondroplasia showed significant increases in height Z-scores and high caregiver satisfaction in a real-world setting.
Where it sits
this study against the rest of the vosoritide corpusSummary and findings
This study evaluated the effectiveness and safety of vosoritide in children with achondroplasia across various Latin American countries. A total of 52 patients were treated for a mean duration of 539 days, with significant increases in height Z-scores observed. Caregiver-reported outcomes indicated high satisfaction with the treatment.
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.
Background
This paper addresses the effectiveness of vosoritide, a C-type natriuretic peptide analog, in treating achondroplasia, a condition characterized by short stature and complications from a genetic mutation. Prior clinical trials have suggested efficacy, but real-world evidence is necessary to understand its performance in diverse healthcare settings. This study aims to fill that gap by analyzing treatment outcomes in a multinational cohort.
Methods
A retrospective, multicenter, multinational cohort study was conducted involving children with molecularly confirmed achondroplasia treated with vosoritide. A total of 52 patients were included, with a mean age of 5.9 years at treatment initiation. The study assessed treatment duration, anthropometric evaluations, annualized growth velocity, adverse events, and caregiver-reported outcomes over a mean treatment duration of 539 days.
Results
The primary endpoint showed that height Z-scores increased significantly from 0.33 at 6 months to 1.58 at 36 months, with p-values ranging from <0.001 to <0.05. All patients demonstrated gains in linear growth, and the annualized growth velocity was consistently higher during treatment compared to before. Adverse events were reported as frequent but mild, primarily injection-site reactions.
Interpretation
The findings suggest that vosoritide can lead to significant increases in height Z-scores in children with achondroplasia, which aligns with previous clinical trial results. However, the effect size may not be clinically meaningful for all patients, and the small sample size limits the generalizability of the results. The retrospective nature of the study and potential biases should be considered when interpreting the outcomes.
Key findings
- Height Z-scores increased from 0.33 at 6 months to 1.58 at 36 months, p<0.001 to p<0.05.
- Mean treatment duration was 539 days.
- 93.9% of patients had high adherence with no treatment interruptions.
- All patients showed gains in linear growth, with some exceeding the 95th percentile for annualized growth velocity.
- 98% of caregivers reported positive changes in their children's overall well-being.
Limitations
- Retrospective study design may introduce biases.
- Sample size of 52 may not represent the broader population.
- No severe adverse events reported, but safety profile based on mild events only.
- Lack of control group limits comparative analysis.