ESPE Abstracts

Background: Achondroplasia is the most common form of osteochondrodysplasia, characterized by abnormal bone and cartilage growth leading to dwarfism and short limbs. It is caused by autosomal dominant mutations in the FGFR3 gene, leading to constitutive activation of the FGFR3 receptor, inhibiting chondrocyte proliferation and disrupting normal bone growth. Vosoritide is a 39-amino acid CNP peptide analogue, indicated for treating achondroplasia in patients over 4 months old until growth plate closure. Administered subcutaneously once daily, vosoritide mimics CNP by binding to NPR-B receptors and inhibiting the FGFR signaling pathway, promoting endochondral and bone growth.

Methods: A prospective observational study was conducted at the Pediatric Endocrinology Unit of the University Hospital of Catania. The study evaluated the efficacy and safety of vosoritide in 10 children with achondroplasia over 3 and 6 months. Auxological parameters, including total height, sitting height, arm span, and growth velocity, were measured and compared to baseline values. Compliance and treatment experience were assessed through a caregiver questionnaire. The dosage was 15 μg/kg, administered subcutaneously daily.

Results: Preliminary results showed a significant increase in growth velocity, with an average increase of 81% at 3 months and 80.7% at 6 months compared to baseline. Height Z-scores also improved, with an average increase of 0.149 at 6 months. Sitting height and arm span showed incremental improvements of 3.4% and 5.5% respectively at 6 months. The proportion between upper and lower body segments remained stable, indicating proportional growth. No significant adverse effects were reported. Laboratory parameters showed no significant changes, indicating a good safety profile. The caregiver questionnaire indicated high compliance, with 89% reporting no missed doses and positive impacts on the children's quality of life.

Discussion: Vosoritide has demonstrated significant efficacy in increasing growth velocity and improving height Z-scores in children with achondroplasia, with a favorable safety profile. The study's findings confirm vosoritide's role as a precision therapy for achondroplasia. Early and prolonged treatment may enhance skeletal growth and overall clinical outcomes, suggesting that earlier initiation of therapy could lead to better results. Future studies should explore vosoritide's long-term effects on skeletal growth, unknown side effects, and its impact on complications and quality of life. Additionally, ongoing trials are investigating vosoritide's efficacy in other conditions, specifically Turner syndrome and idiopathic short stature. In conclusion, vosoritide offers a promising treatment option for achondroplasia, with ongoing research needed to fully understand its long-term benefits and optimize its use in clinical practice.