UX143 (setrusumab): Monoclonal Antibody for Osteogenesis Imperfecta (OI)

OI: a group of genetic disorders impacting bone metabolism

Approximately 85% to 90% of OI cases are caused by mutations in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. As collagen represents the foundation upon which bone is formed, patients with OI have increased bone resorption (breakdown of old bone) and inadequate production of new bone, which leads to decreased bone mass, bone fragility and weakness. Patients with OI experience bone brittleness, which leads to a high rate of fractures, including at atypical sites, bone deformities, including abnormal spine curvature, pain, decreased mobility and short stature. No treatments are approved for OI, which affects approximately 60,000 people in the developed world.

Evaluating UX143 (setrusumab) to improve bone formation and density

UX143 is an investigational fully-human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway and inhibits the activity of bone-forming cells. By blocking the inhibitory effects of sclerostin, UX143 is designed to increase bone formation and density, increase the production of collagen, and increase bone mineral density and strength. Sclerostin inhibition also reduces excessive bone resorption, further improving bone density.

Mereo BioPharma completed the Phase 2b ASTEROID study of UX143 in adults with OI, which demonstrated a dose-dependent increase in bone formation, density and strength, and improvements in serum P1NP (procollagen type I N propeptide), a biomarker of bone formation and direct measure of collagen production. Ultragenyx plans to conduct a Phase 2/3 study of UX143 in pediatric patients with OI and a pivotal study in adult patients with OI.

UX143 was granted Orphan Drug Designation in the United States and EU and rare pediatric disease designation in the United States and accepted into the European Medicine Agency’s Priority Medicines program (PRIME).

UX143 is being developed under a collaboration and license agreement between Mereo BioPharma and Ultragenyx.

Learn more about UX143 clinical studies