ESPE Abstracts

Background: Achondroplasia, the most prevalent skeletal dysplasia in children, is a multisystemic disease resulting from a common mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. This mutation disrupts endochondral ossification, leading to disproportionate short stature. Historically, management has been primarily supportive due to the absence of targeted therapies. However, recent advancements have led to clinical trials for potential treatments, resulting in the approval of Vosoritide, the first precision therapy for achondroplasia. Despite its approval, limited real-world data on Vosoritide use exists in the MENA region. This study aims to present our single-center experience with Vosoritide in children with achondroplasia, assessing its efficacy, safety, and practical considerations.

Methods: The study enrolled 11 participants aged 1.6 to 14 years, diagnosed with achondroplasia, seen at the combined endocrine-genetic clinics at Sidra Medicine between 2022 and 2023. Inclusion criteria included molecularly confirmed achondroplasia and age from 4 months to growth plate closure. Patients received Vosoritide (15•0 μg/kg subcutaneous once daily) after thorough parental education and medical supervision. Follow-up visits occurred at month 1, 3, and 6, then every 6 months, later increased to every 3 months for better monitoring. Primary outcomes included changes in height and growth velocity, to baseline, and observed side effects.

Results: Preliminary data from 9 of the initial 11 patients were analyzed. Two from the 11 patients were excluded due to a short duration of Vosoritide use (2 months). Statistical analysis using SPSS 27 revealed a significant effect of Vosoritide on height (p-value 0.040). Regarding growth velocity, compliance significantly impacted results. Among compliant patients, growth velocity increased by an average of 2.5 cm/year (1-5 cm/year) from baseline. One patient who started Vosoritide before the age 2 years showed no significant growth velocity increase after 6 months (may be explained by short duration, or by the rapid declining growth velocity in very young children with achondroplasia). All patients experienced self-limiting side effects, primarily injection site redness, with no serious adverse effects noted. Non-compliance was mainly attributed to the burden of daily injections.

Conclusion: Our single-center experience demonstrates Vosoritide's positive impact on height increase in achondroplasia patients, particularly with adherence and early initiation before growth plate closure. Challenges in Vosoritide use, including daily injections, were noted. Minimal and self-limiting side effects were observed. Further studies with larger samples and longer follow-up periods are necessary to validate these findings and ascertain long-term efficacy and safety in this population.