Slipped Capital Femoral Epiphysis during Vosoritide Therapy for Short Stature: A Case Series.

INTRODUCTION

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.

CASE REPORT: 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.

CONCLUSION

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.