Introduction:
Achondroplasia is the most common form of skeletal dysplasia. Individuals with achondroplasia may suffer from a range of serious and debilitating complications over the course of their lifetime: sleep disordered breathing, upper airway obstruction and ear, orthopedic problems, foramen magnum stenosis, among others. Recently, Several drugs that modulate abnormally activated FGFR3 signaling have recently emerged, being vosoritide, a recombinant C-type natriuretic peptide (CNP) analog, the first specific drug approved for children with achondroplasia

 

Methods:
Data from a cohort of Brazilian patients with achondroplasia under therapy with vosoritide on a single center for rare diseases for 3 year period were analyzed. All available retrospective medical records of anthropometry (length/height, weight, occipitofrontal circumference), surgery, polysomnography (PSG), and imaging (e.g., X-ray, magnetic resonance imaging) were included.

 

Results:
Data from 18 patients (60% female; mean age 4.5 years) pre and post treatment were compared when available. The youngest patient to start therapy was a 16 month female and the one showing the best change in curve growth and facial bone structure.  Increase of growth velocity was seen in all patients, nevertheless the improvement was significantly higher in the group starting therapy under 3 years of age. None of the patients that started therapy under 2 years of age developed foramen magnus stenosis nor recurrent ear/upper airway infections sleep. All patients showed improvement in hypotonia and had better acquisition of milestones. No worsening in sleep study indices was observed with vosoritide, in fact most sleep study indices indicated small numerical improvements on vosoritide specially in the patients that started under 3 years of age.  In total, 10 mild adverse events were reported during the study period. No serious adverse events were reported even in the youngest group; no injection site reaction was reported.

 

Conclusion:
Besides improving growth velocity, vosoritide therapy showed greater changes in facial volume, facial sinus volume and great aperture area, in particular patients under 3 years of age. Overall, our findings suggest that vosoritide therapy also had clinical impact in terms of improved ventilation, a reduced risk of recurrent respiratory infections and even a reduced risk of death in infancy in patients with achondroplasia due to apnea.