UX143
for OI
UX143 (setrusumab): Monoclonal antibody for the potential treatment of osteogenesis imperfecta (OI) Types I, III and IV
Program overview
Stage: Phase 3
Disease: OI, also known as brittle bone disease or glass bones disease
Prevalence: 60,000 people in commercially accessible geographies
Disease Mechanism: A heterogenous group of congenital bone disorders resulting from a change in a gene that impacts type I collagen.
Symptoms: Bone fragility, fractures, low bone mass, skeletal deformity, pain, short stature, decreased independent ambulation
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
Osteogenesis Imperfecta (OI) includes a group of genetic disorders impacting bone metabolism. Approximately 85% of OI cases are caused by a genetic variant in the COL1A1 or COL1A2 genes, leading to reduced or abnormal collagen. Patients with OI exhibit inadequate production of new bone and excess bone resorption, resulting in decreased bone mineral density, bone fragility and weakness. OI can also lead to bone deformities, abnormal spine curvature, pain, decreased mobility, and short stature. No treatments are globally approved for OI, which affects approximately 60,000 people in commercially accessible geographies.
Evaluating UX143 to reduce fracture rate and improve quality of life
UX143 (setrusumab) is an investigational, fully human monoclonal antibody that inhibits sclerostin; sclerostin is a negative regulator of bone formation. Inhibiting sclerostin is expected to increase new bone formation, bone mineral density and bone strength in OI.
Mereo BioPharma completed the Phase 2b Asteroid study of UX143 in adults with OI. Ultragenyx is developing UX143 in pediatric and young adult patients across OI sub-types I, III and IV with two late-stage trials: the pivotal Phase 2/3 Orbit study and Phase 3 Cosmic study. The global, seamless Phase 2/3 Orbit study is evaluating the effect of UX143 compared to placebo on annualized fracture rate in patients aged 5 to <26 years. The global Phase 3 Cosmic study is an open-label, randomized, active-controlled study evaluating the effect of UX143 compared to intravenous bisphosphonate (IV-BP) therapy on annualized fracture rate in patients aged 2 to <7 years. Based on primary analysis of 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 Breakthrough Therapy Designation 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.