Vosoritide

Voxzogo

Vosoritide is a 39-amino-acid analog of C-type natriuretic peptide (CNP), a signaling peptide that regulates bone growth at the growth plate. It was engineered from native CNP by modifying the N-terminus to resist degradation by the enzyme neutral endopeptidase, extending its half-life enough to permit once-daily subcutaneous dosing while preserving activity at its receptor, natriuretic peptide receptor-B (NPR-B). Vosoritide targets the root biology of achondroplasia, the most common form of disproportionate short stature. Achondroplasia is caused by a gain-of-function mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which makes FGFR3 overactive. Overactive FGFR3 suppresses the proliferation and maturation of cartilage cells in the growth plate, limiting the bone lengthening that drives height. CNP signaling through NPR-B naturally opposes FGFR3 by inhibiting a downstream part of the same pathway (the MAPK cascade). By supplying a stabilized CNP analog, vosoritide restores this counter-signal, relieving the brake FGFR3 places on the growth plate and increasing growth velocity. Vosoritide was approved by the FDA in 2021 (Voxzogo) to increase linear growth in children with achondroplasia who have open growth plates (epiphyses), initially for children five and older and later extended to younger ages in various regions. In clinical trials it produced a meaningful increase in annual growth velocity compared with placebo. Because CNP is related to the natriuretic peptides that affect blood pressure, transient drops in blood pressure can occur, so children are appropriately hydrated and fed before dosing and monitored. It is a specialist pediatric medicine given by daily subcutaneous injection under the care of clinicians experienced in skeletal dysplasias; long-term effects on final adult height and function continue to be studied.