ESPE Abstracts

Vosoritide is a C-type Natriuretic Peptide (CNP) analogue therapy for treatment of achondroplasia. Vosoritide acts on growth plate chondrocytes through the Natriuretic Peptide Receptor-B to stimulate increased endochondral bone growth, leading to increased growth velocity in treated subjects. In Phase II clinical studies, subject blood and urine samples were analyzed to monitor putative bone growth biomarkers including cross-linked C-terminal telopeptides of collagen II (CTxII), Bone-Specific Alkaline Phosphatase (BSAP), N-terminal pro-peptide of collagen I (PINP), and an N-terminal fragment of Collagen X (CXM). While all of the biomarkers analyzed were variable, CXM demonstrated dose-dependent increases, BSAP appeared to increase slightly over time on treatment for all dose levels, and there was no apparent trend or dose dependent response for CTxII or P1NP. Based on these results, BSAP and CXM were incorporated into the placebo-controlled Phase III vosoritide clinical study 111-301 and pre-treatment natural history study 111-901. The Phase III study data confirmed that CXM was increased in subjects that received vosoritide, but not placebo, while differences in BSAP between vosoritide and placebo groups were small. Overall, the data from vosoritide clinical studies suggest that CXM is superior to CTxII, PINP, and BSAP for monitoring changes in endochondral bone growth.