Vosoritide is a Recombinant CNP Analog, That Binds to NPR-B and Reduces FGFR3 Activity

Achondroplasia is a genetic disorder that results in impaired endochondral bone growth. The characteristic of the disease is short arms and legs. The cause is the overactive FGFR3 (fibroblast growth factor receptor 3). The protein contributes to the production of collagen and other structural components in tissues and bones. Furthermore, the mutation leads to excess inhibition of chondrocyte proliferation and differentiation in the physis of long bones.

Natriuretic peptides are a family of three structurally related hormone/paracrine factors, including Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). These peptides have natriuretic, diuretic, and vasodilating activities. These three peptides have corresponding binding receptors, natriuretic peptide receptors (NPR), containing NPR-A, NPR-B and NPR-C. NPR-B appears to be activated preferentially by CNP.

Vosoritide is a recombinant CNP analog, that binds to NPR-B and reduces FGFR3 activity.

From: Legeai-Mallet L, Savarirayan R. Bone. 2020 Dec;141:115579.

Vofatamab is a monoclonal antibody that acts by binding to the extracellular domain of FGFR3 and blocking ligand binding. Firstly, according to in vitro experiments, Vosoritide decreases NPR-B phosphorylation in chondrocytes. Also, it reduces ERK1/2 activation in ACH growth-plate chondrocytes. Besides, Vosoritide improves chondrocyte differentiation and increases the proliferative growth plate area of cultured Fgfr3Y367C/+ femurs.

Moreover, Vosoritide has also shown remarkable efficacy in Fgfr3-mutant animal models. In Fgfr3Y367C/+ mice, this agent results in phenotypic changes including flattening of the skull, elongation of the snout, and improvement of the anterior crossbite. Except for these appearances, Vosoritide-treated mice show larger paws and digits, and longer and straightened tibias and femurs as well. Therefore, these researches suggest that Vosoritide is effective in the treatment of FGFR3-mutant achondroplasia.

In conclusion, Vosoritide is a recombinant CNP analog, which reduces FGFR3 activity, possessing the great potential to treat Achondroplasia.


1. Duggan S. Drugs. 2021 Nov;81(17):2057-2062.
2. Shuhaibar LC, Legeai-Mallet L, et al. JCI Insight. 2021 May 10;6(9):e141426.
3. Lorget F, Legeai-Mallet L, et al. Am J Hum Genet. 2012 Dec 7;91(6):1108-14.