Vosoritide improves linear and appendicular growth in real-world achondroplasia cohort, including post-surgical patients

Achondroplasia is a rare autosomal dominant disorder caused by a gain-of-function mutation in the FGFR3 gene, leading to impaired endochondral ossification and short stature. Vosoritide, a C-type natriuretic peptide analogue, is the first approved therapy, acting by activating the NPR-B receptor to inhibit the overactive FGFR3 signaling pathway. While clinical trials established its efficacy, real-world data, particularly for patients with prior orthopedic surgeries often excluded from trials, remained limited, posing a gap in understanding its broader applicability.

This retrospective cohort study analyzed 25 children with achondroplasia (17 boys, age range 2.9-14.3 years) treated with vosoritide for a mean duration of 12.7 months at a single multidisciplinary center. The primary outcome involved calculating Δ z-scores for height, sitting height, arm span, and body mass index (BMI) from baseline to follow-up. An AI-assisted growth assessment tool, previously validated for achondroplasia, was used for z-score calculations. Multiple linear regression analyses were performed to assess potential predictors of treatment response, and a subgroup analysis compared patients with and without prior limb-lengthening surgery.

Vosoritide therapy significantly enhanced linear and appendicular growth in the real-world cohort. Mean height z-scores improved from -0.62 ± 1.09 at baseline to -0.24 ± 1.20 at follow-up (P < .001). Similarly, mean arm span z-scores increased from -1.28 ± 0.93 to -0.96 ± 0.91 (P = .007). Sitting height z-scores showed a non-significant trend toward improvement, while BMI z-scores remained stable throughout the treatment period. The mean gains in Δ height and Δ arm span z-scores were +0.38 ± 0.45 and +0.32 ± 0.48, respectively.

A subgroup analysis of 8 patients with prior limb-lengthening surgery versus 17 without showed no significant differences in growth outcomes, indicating efficacy across diverse clinical profiles. Regression analyses, adjusted for sex, age, BMI z-scores, and surgical history, were likely underpowered to detect meaningful predictors of response. Importantly, no serious treatment-related adverse events were reported.