The role and efficacy of vosoritide

Voxzogo (vosoritide) is an analog of C-type natriuretic peptide that promotes bone growth to counteract growth inhibition in children with achondroplasia. Urinary cyclic guanosine monophosphate (cGMP) and serum type X collagen marker (CXM) were both elevated after daily administration of vosoritide and serve as biomarkers demonstrating increased endochondral bone growth, with cGMP indicating NPR-B binding activity and CXM indicating bone metabolism.

Achondroplasia is a congenital disease caused by missense mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a gain-of-function that negatively regulates endochondral bone growth. Under normal circumstances, FGFR3 is expressed during both embryonic and postnatal development, but plays a different role in each developmental process. During initial development, FGFR3 signaling promotes the proliferation (i.e., growth) of chondrocytes, whereas postnatal bone growth is actually inhibited by FGFR3—thus, the pathological activation of FGFR3 observed in patients with achondroplasia results in inhibited bone growth before puberty.

Vosoritide, the main ingredient in Voxzogo, is an analog of C-type natriuretic peptide (CNP), a signaling molecule that appears to be primarily responsible for stimulating the growth of cartilage cells and long bones. CNP (or vosoritide) binds to its corresponding receptor NPR-B, generating a signaling cascade that ultimately inhibits the MAPK/ERK pathway by inhibiting RAF-1 and stimulates chondrocyte proliferation and differentiation. This activity serves to antagonize downstream signaling produced by FGFR3 and its effects on bone growth.

Although relatively well tolerated, transient episodes of hypotension were observed in clinical studies. Patients with preexisting cardiovascular disease and those taking antihypertensive medications were excluded from clinical trials. Making sure you drink enough food and fluids before taking vosoritide can reduce the risk of hypotension.