Rua Inês B, Silva Isabel, Beger Christoph, Gomes Cristina, Pais Maria J, Mirante Alice, Sousa Sérgio B
Pediatric Endocrinology, Diabetes and Growth Department, Bone Dysplasia Multidisciplinary Team (ERN-BOND), Pediatric Hospital, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Medical Genetics Department, Bone Dysplasia Multidisciplinary Team (ERN-BOND), Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal.
Adv Ther. 2025 Jun 5. doi: 10.1007/s12325-025-03223-6.
Achondroplasia, the most common skeletal dysplasia, is caused by autosomal dominant gain-of-function pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Vosoritide, a C-type natriuretic peptide analog, is a first-in-class targeted treatment for achondroplasia that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth. This retrospective cohort study evaluated growth, safety, and treatment compliance in children with achondroplasia receiving vosoritide under an early access program in Portugal.
Twenty-seven children aged 2-14 years with a genetically confirmed diagnosis of achondroplasia were treated with vosoritide at a single Portuguese center for at least 6 months between January 2022 and June 2024. The analysis included children with severe achondroplasia-associated complications. Anthropometric measurements collected to characterize the effect of vosoritide on growth included height standard deviation score (SDS) and annualized growth velocity (AGV). Student's t test was used for statistical comparisons. Safety and tolerability endpoints included adverse drug reactions and treatment adherence.
In total, 15 children completed at least 24 months of treatment. After 24 months of treatment, mean variation in height SDS increased from baseline by + 0.95 SD (P ≤ 0.0001), referenced to an untreated achondroplasia-specific population, and + 0.56 SD (P ≤ 0.0001) relative to children of average stature. Additionally, mean AGV from baseline was 5.87 cm/year (95% confidence interval 5.14-6.60), resulting in a significant increase of + 1.62 cm/year (P ≤ 0.0001). Injection site reactions were the most common adverse drug reaction observed (n = 14); no serious adverse drug reactions were reported. There were no discontinuations due to adverse drug reactions.
Vosoritide showed long-term effectiveness in a real-world Portuguese population of patients with achondroplasia. Vosoritide was also well tolerated, and patients showed good adherence to treatment. These findings were consistent with the outcomes of clinical trials and existing real-world experience.
软骨发育不全是最常见的骨骼发育不良，由成纤维细胞生长因子受体3（FGFR3）基因的常染色体显性功能获得性致病变异引起。伏索利肽是一种C型利钠肽类似物，是治疗软骨发育不全的首个靶向治疗药物，可对抗过度活跃的FGFR3信号传导，以刺激软骨内骨生长。这项回顾性队列研究评估了葡萄牙早期准入项目中接受伏索利肽治疗的软骨发育不全儿童的生长情况、安全性和治疗依从性。
2022年1月至2024年6月期间，27名年龄在2至14岁、经基因确诊为软骨发育不全的儿童在葡萄牙的一个中心接受了至少6个月的伏索利肽治疗。分析纳入了患有严重软骨发育不全相关并发症的儿童。为了描述伏索利肽对生长的影响而收集的人体测量数据包括身高标准差评分（SDS）和年化生长速度（AGV）。采用学生t检验进行统计比较。安全性和耐受性终点包括药物不良反应和治疗依从性。
共有15名儿童完成了至少24个月的治疗。治疗24个月后，身高SDS的平均变化较基线增加了+0.95标准差（P≤0.0001），以未治疗的软骨发育不全特定人群为参照，相对于平均身高的儿童增加了+0.56标准差（P≤0.0001）。此外，基线时的平均AGV为5.87厘米/年（95%置信区间5.14-6.60），导致显著增加了+1.62厘米/年（P≤0.0001）。注射部位反应是观察到的最常见的药物不良反应（n=14）；未报告严重药物不良反应。没有因药物不良反应而停药的情况。
伏索利肽在葡萄牙软骨发育不全患者的真实世界人群中显示出长期有效性。伏索利肽的耐受性也良好，患者对治疗表现出良好的依从性。这些发现与临床试验结果和现有的真实世界经验一致。
