Impact of Vosoritide on Growth in Pediatric Patients with Achondroplasia and Hypochondroplasia (Off-Label Use): Experience from Two Mexican Referral Centers

Abstract

Introduction

FGFR3-related skeletal dysplasias (SDs) are growth disorders characterized by disproportionate short stature and impaired endochondral ossification. Achondroplasia is the most common skeletal dysplasia, whereas hypochondroplasia generally presents with a milder phenotype. Vosoritide, a C-type natriuretic peptide analog, acts as a disease-modifying therapy by counteracting overactivation of the FGFR3 signaling pathway, thereby increasing growth velocity (GV) in patients with achondroplasia. However, there are few reports from Latin America regarding clinical experience with this treatment, and data on its use in other FGFR3-related skeletal dysplasias remain scarce.

Objective

To describe growth outcomes in four patients with skeletal dysplasias treated with vosoritide at two Mexican referral centers.

Methods

A retrospective case series of four patients with skeletal dysplasias treated with vosoritide was conducted. Age at treatment initiation, height, growth velocity (GV), and adverse events (AEs) during follow-up were analyzed.

Results

Patient 1: Female with achondroplasia (FGFR3 c.1138G>A, heterozygous). Vosoritide was initiated at 9 years and 4 months of age. Height increased from 101 cm at treatment initiation to 111 cm after 19 months of follow-up (+10 cm). Pre-treatment GV was 3.75 cm/year and increased to 6.32 cm/year following treatment, representing a 65.8% increase. Mild injection-site pain was reported as an adverse event.

Patient 2: Male with achondroplasia (FGFR3 c.1138G>A, heterozygous). Vosoritide was initiated at 9 years and 8 months of age. Estimated GV increased from 1.7 cm/year during the pre-treatment period to 2.7 cm/year after treatment initiation, representing an approximately 58% increase. Mild injection-site pain was documented as an adverse event.

Patient 3: Male with achondroplasia (FGFR3 c.1138G>A, heterozygous). Vosoritide was initiated at 6 years and 11 months of age. During 12 months of follow-up, height increased from 84 cm to 92 cm, with a total gain of 8 cm and an estimated GV of 8.0 cm/year. Hypertrichosis of the extremities was reported as an adverse event and resolved spontaneously.

Patient 4: Male with hypochondroplasia (FGFR3 c.1620C>G, heterozygous). Vosoritide was initiated at 11 years and 5 months of age (off-label use). Height increased from approximately 112.7 cm at treatment initiation to 120 cm at last follow-up (approximately +7.2 cm). Estimated GV increased from 3.8 cm/year during the pre-treatment period to 5.0 cm/year over 17.3 months of follow-up, representing an approximately 32% increase. Mild injection-site pain was documented as an adverse event.

Conclusions

In this case series, vosoritide treatment was associated with increased growth velocity and favorable tolerability. These findings are consistent with those reported in international clinical studies and support its role as a disease-modifying therapy in patients with achondroplasia and hypochondroplasia.