ESPE Abstracts

Background: Vosoritide is a biological analogue of C-type natriuretic peptide, which promotes endochondral ossification by suppressing FGFR3 downstream signaling in achondroplasia (ACH). It is the first drug targeting the pathophysiology of ACH and was launched in Japan in August 2022, for the first time in the world without a minimum age limit. There have been no reports on the efficacy and safety of vosoritide other than clinical trials.

Materials and Methods: To evaluate the efficacy and safety of vosoritide therapy in patients with ACH at our hospital. The study was conducted retrospectively using the medical records of 16 ACH patients who started vosoritide therapy between November 2022 and March 2024.

Results: All patients had a genetic diagnosis of FGFR3:G360R before starting therapy. The median age at treatment initiation was 29 months (range 1-106 months), and all patients were prepubertal. Three patients switched from growth hormone (GH) therapy to vosoritide, and four patients were postoperative for foramen magnum stenosis or hydrocephalus. Vosoritide was discontinued in one patient who developed compensatory shock after the first dose of vosoritide. Height standard deviation (SD) values (n = 13) and height growth velocity (HGV) SD values (n = 10) were calculated for patients treated with vosoritide for more than six months based on the standard height and HGV of previously reported ACH. Height SD values and arm span to height ratio improved during the treatment period. On the other hand, HGV SD showed no significantly difference between pre- and post-treatment. Of the five patients with reduced HGV SD, two changed from GH therapy and two had previous surgery. Non-mild side effects were observed in three patients; the symptoms were compensatory shock in a three- month-old infant, pallor and vomiting in a three-month-old infant, and bad feeling and vomiting after influenza in a six-year-old girl, all of which appeared within about 30 minutes after administration.

Discussion: Vosoritide improves height SD values in ACH as previously reported, and it was newly found to improve the arm span to height ratio was also newly found to be improved. GH therapy in ACH has been reported to improve growth rate for several years after introduction and may provide better HGV than vosoritide during this period. Side effects may be due to vasodilatation of vosoritide and may be particularly risky in infants.