ESPE Abstracts

Introduction: Achondroplasia is caused by a pathogenic mutation in the FGFR3 gene, leading to impaired endochondral bone growth and multiple medical complications. Vosoritide (once daily, subcutaneous injection) has recently been approved by the European Medicines Agency (EMA) for treating achondroplasia in patients aged ≥2 years until closure of epiphyses. It has been made available in France via an early access program, a cohort Temporary Authorization for Use (ATU). We report on the early experiences (baseline clinical characteristics, initiation process and safety) of patients enrolled in the ATU within the French Centre of Reference for skeletal dysplasia (CRMR MOC) network.

Methods: The ATU was initiated on 24th June 2021. A consortium of French achondroplasia experts belonging to the CRMR MOC reviewed the ACH cases followed in the network, to confirm eligibility for treatment initiation. Scale up with prioritization of the oldest patients was proposed, within the children with achondroplasia aged ≥5 years with open epiphyses. After treatment initiation and parent therapeutic education, the patient follow up includes visits at month 1, 3 and 6 and at 6-monthly intervals thereafter. Data are systematically collected to evaluate treatment compliance, adverse events and growth.

Results: The first patient enrolled in the ATU on 27th of September 2021, and at the time of data-cut (13 December 2021), 29 patients were enrolled from 6 centers across France. At the start of treatment (baseline), 52% of patients were female with a mean age of 9 years, ranging between 7 and 13 years. The mean height was 106.9 cm (range 92.0- 119.5 cm) with height z-scores ranging between -3.9 and -7.7 in males and -3.4 and -6.0 in females. Mean weight was 26.2 kg (16.8-60.8kg). No enrolled patients discontinued treatment and compliance was 100% with no patients reporting any missed doses. In total, there were 12 adverse events (AEs) reported among 7 patients. The majority of AEs were mild and included injection site reactions and vomiting, with the most common being injection site rash (4 events). There were no serious adverse events related to vosoritide treatment, and no AEs led to permanent treatment discontinuation.

Conclusions: Over a 3-month period in a real-world setting, the overall safety profile of vosoritide in children with achondroplasia was consistent with that observed in clinical trials. Ongoing monitoring and data collection from this early access program will be useful to establish the ongoing safety and effectiveness of vosoritide in the real world.