Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 11:71:102591.
doi: 10.1016/j.eclinm.2024.102591. eCollection 2024 May.

Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

Andrew Dauber  1   2 , Anqing Zhang  3 , Roopa Kanakatti Shankar  1   2 , Kimberly Boucher  1 , Tara McCarthy  1 , Niusha Shafaei  1 , Raheem Seaforth  1 , Meryll Grace Castro  1 , Niti Dham  2   4 , Nadia Merchant  1   2
Affiliations

Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

Andrew Dauber et al. EClinicalMedicine. .

Abstract

Background: Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.

Methods: We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007).

Findings: Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity.

Interpretation: Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia.

Funding: This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.

Keywords: C-type natriuretic peptide; CNP; FGFR3; Hypochondroplasia; Vosoritide.

PubMed Disclaimer

Conflict of interest statement

AD and NM have served as consultants for BioMarin, but all compensation has been paid to Children's National Hospital and neither author has received any personal compensation from BioMarin. AD received an investigator-initiated grant from BioMarin to fund the current study. RKS has received an investigator-initiated grant from BioMarin to fund a study of vosoritide in girls with Turner syndrome. The remaining authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2
Annualized growth velocity.
Fig. 3
Fig. 3
Annualized growth velocity SDS.
Fig. 4
Fig. 4
Standing height SDS.
Fig. 5
Fig. 5
Collagen X biomarker (CXM) levels.
Fig. 6
Fig. 6
Maximum change in urine cGMP levels from baseline.
Fig. 7
Fig. 7
Time course of change in urine cGMP levels.
See this image and copyright information in PMC

References

    1. Andersen P.E., Hauge M. Congenital generalised bone dysplasias: a clinical, radiological, and epidemiological survey. J Med Genet. 1989;26(1):37–44. doi: 10.1136/jmg.26.1.37. - DOI - PMC - PubMed
    1. Stevenson D.A., Carey J.C., Byrne J.L.B., Srisukhumbowornchai S., Feldkamp M.L. Analysis of skeletal dysplasias in the Utah population. Am J Med Genet A. 2012;158A(5):1046–1054. doi: 10.1002/ajmg.a.35327. - DOI - PubMed
    1. Bober M.B., Bellus G.A., Nikkel S.M., Tiller G.E. Hypochondroplasia. GeneReviews®. 1993. http://www.ncbi.nlm.nih.gov/pubmed/19622626
    1. Arenas M.A., Del Pino M., Fano V. FGFR3-related hypochondroplasia: longitudinal growth in 57 children with the p.Asn540Lys mutation. J Pediatr Endocrinol Metab. 2018;31(11):1279–1284. doi: 10.1515/jpem-2018-0046. - DOI - PubMed
    1. Bellus G.A., McIntosh I., Anne Smith E., et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995;10(3):357–359. doi: 10.1038/NG0795-357. - DOI - PubMed

Associated data