for OI

UX143 (setrusumab): Monoclonal antibody for the potential treatment of osteogenesis imperfecta (OI)

Program overview

Stage: Phase 2/3
Disease: OI, also known as brittle bone disease
Prevalence: 60,000 people in our territories
Disease Mechanism: A group of inherited bone disorders resulting from a defect in genes that impact bone formation.
Symptoms: Bone fragility, fractures, deformities, pain, short stature, impairment, loss of mobility
Treatment Modality: Fully human monoclonal antibody
Treatment Mechanism: Inhibit sclerostin

OI: Abnormal bone metabolism leads to decreased bone mass, and increased bone fragility and weakness

Approximately 80% to 85% of OI cases are caused by variants 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, individuals with OI have increased bone resorption (breakdown of old bone) and inadequate or abnormal production of new bone, which leads to decreased bone mass and causes bone fragility and weakness. Individuals 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. There are no FDA or EMA approved treatments for OI, which affects approximately 60,000 people in our territories.

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 selectively binding to and inhibiting 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 has initiated a late-stage clinical development program that includes two ongoing studies. First is the pivotal Phase 2/3  Orbit study, which is evaluating the effect of UX143 compared to placebo on annualized clinical fracture rate in patients aged 5 to <26 years. Second is the Phase 3 Cosmic study, an active-controlled study evaluating UX143 compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <7 years. Based on primary results from the dose-selection Phase 2 portion of the Phase 2/3 Orbit study, a dose of 20 mg/kg was selected for investigation in both of the Phase 3 studies.

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.

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