Slipped Capital Femoral Epiphysis during Vosoritide Therapy for Short Stature: A Case Series.
Vosoritide therapy may be linked to an increased risk of slipped capital femoral epiphysis in some children with genetic short stature, particularly those with Turner syndrome and Aggrecan mutations.
Where it sits
this study against the rest of the vosoritide corpusSummary and findings
This case series reports on the occurrence of slipped capital femoral epiphysis (SCFE) in five participants undergoing vosoritide therapy for genetic short stature. All participants had received treatment for more than 12 months. SCFE was observed in specific genetic subgroups, including those with Aggrecan mutations and Turner syndrome.
Abstract
<h4>Introduction</h4>Vosoritide is a C-type natriuretic peptide analog approved for treatment of children with achondroplasia with established safety and efficacy. We report slipped capital femoral epiphysis (SCFE) as a treatment-emergent serious adverse event in two prospective clinical trials of vosoritide for individuals with genetic forms of short stature.<h4>Case report</h4>We report 5 participants from two investigator-initiated, single center, phase II, prospective, open label clinical trials of vosoritide (NCT04219007 Basket trial including patients with RASopathies, Aggrecan mutations (ACAN) and NPR2 deficiency and NCT05849389 in girls with Turner syndrome) who developed SCFE. In the basket trial, SCFE was observed in 2/12 participants with ACAN mutations, 1/11 with RASopathy but not in the 7 participants with NPR2 mutations or 24 with hypochondroplasia. In the Turner syndrome trial, 2/5 participants receiving vosoritide developed SCFE. All 5 participants who developed SCFE had received >12 months of treatment and presented with the rare valgus type of SCFE.<h4>Conclusion</h4>Vosoritide treatment may be associated with a higher risk of SCFE in some individuals with genetic forms of short stature such as Turner syndrome and Aggrecan mutations. The causal mechanisms and contributory factors to the predisposition for valgus deformities noted with vosoritide therapy in children with these genetic conditions warrant further study.
Background
This paper addresses the potential adverse effects of vosoritide, a C-type natriuretic peptide analog, in children with genetic short stature. Prior knowledge indicated that vosoritide is approved for treating achondroplasia, with established safety and efficacy. This study is significant as it highlights a serious adverse event, SCFE, that may be associated with the treatment.
Methods
The study is a case series derived from two investigator-initiated, single-center, phase II, prospective, open-label clinical trials. The population included participants with genetic forms of short stature, specifically those with ACAN mutations, RASopathy, and Turner syndrome. The duration of treatment was greater than 12 months, but specific dosing information is not reported in the abstract.
Results
In total, SCFE was reported in 5 participants across the trials. Specifically, SCFE was observed in 2 out of 12 participants with ACAN mutations and 1 out of 11 with RASopathy in the basket trial, while 2 out of 5 participants in the Turner syndrome trial also developed SCFE. All cases presented with the rare valgus type of SCFE.
Interpretation
The findings suggest a potential association between vosoritide therapy and an increased risk of SCFE, particularly in individuals with specific genetic conditions. While the statistical significance of these findings is not explicitly stated, the clinical implications warrant caution. The small sample size and open-label design limit the ability to draw definitive conclusions about causality.
Key findings
- SCFE observed in 2/12 participants with ACAN mutations in the basket trial.
- SCFE observed in 1/11 participants with RASopathy in the basket trial.
- SCFE not observed in 7 participants with NPR2 mutations.
- SCFE not observed in 24 participants with hypochondroplasia.
- SCFE observed in 2/5 participants receiving vosoritide in the Turner syndrome trial.
Limitations
- small sample size (n=5)
- open-label design may introduce bias
- single-center study limits generalizability
- no control group for comparison
- specific dosing information not reported