Ultragenyx, Mereo BioPharma announce UX143 phase 3 Orbit study for osteogenesis imperfecta

Ultragenyx, Mereo BioPharma announce UX143 phase 3 Orbit study for osteogenesis imperfecta

By, Admin 12 July 2025

Overview

Ultragenyx Pharmaceutical Inc, a biopharma company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare genetic diseases, and Mereo BioPharma Group plc - a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases - announced that the randomized, placebo-controlled phase 3 portion of the Orbit study evaluating UX143 (setrusumab) in pediatric and young adult patients with osteogenesis imperfecta (OI) is progressing toward a final analysis consistent with the original plan, around the end of the year.
The Data Monitoring Committee met and informed the company that UX143 demonstrates an acceptable safety profile and the company should continue the study to the final analysis.

Statement from Emil D. Kakkis: CEO, Ultragenyx

Based on the feedback we hear from investigators and families who participated in the studies, we are confident that increasing bone mass leads to stronger bone, less fractures, and improved physical abilities,” said Emil D. Kakkis, CEO and president of Ultragenyx. “While we had hoped to be able to stop the study early, we look forward to having results from both Orbit and Cosmic clinical around the end of this year.”

About ongoing study

  • Consistent with the statistical analysis plan, data from the Cosmic study were not analyzed at this interim timepoint. Study conduct is going well and safety in this younger patient population is consistent with the safety profile in the other studies.
  • Patients will continue dosing in the ongoing phase 3 Orbit and Cosmic clinical studies with the final analyses to be conducted after patients have been on therapy for at least 18 months. The threshold for the phase 3 Orbit final analysis is p<0.04 and for the phase 3 Cosmic final analysis is p<0.05.

Ultragenyx is developing setrusumab in pediatric and young adult patients across OI sub-types I, III and IV with two late-stage studies: the pivotal phase 2/3 Orbit study and phase 3 Cosmic study.

The phase 2/3 Orbit study

  • The global, seamless phase 2/3 Orbit study is evaluating the effect of setrusumab on clinical fracture rate in patients aged 5 to 25 years. 
  • In the phase 2 portion, 24 patients were randomized 1:1 to receive setrusumab at one of two doses to determine the optimal dosing strategy for Phase 3. 
  • All patients from the 40 mg/kg dosing cohort have been transitioned to 20 mg/kg of setrusumab.

Pivotal phase 3 portion of study

  • The pivotal phase 3 portion of the study has enrolled an additional 159 patients at 45 sites across 11 countries, with subjects randomized 2:1 to receive setrusumab or placebo, and a primary efficacy endpoint of annualized clinical fracture rate. 
  • All patients will transition to an extension period and receive open-label setrusumab after the phase 3 primary analysis is complete.

The global phase 3 Cosmic study

  • The global phase 3 Cosmic study is an open-label, randomized, active-controlled study in patients aged 2 to <7 years. 
  • Patients are randomized 1:1 to receive setrusumab or intravenous bisphosphonates (IV-BP) therapy to evaluate reduction in the annualized fracture rate. 
  • The Cosmic study has enrolled 69 patients at 21 sites across 7 countries.

About the condition Osteogenesis Imperfecta

  • Osteogenesis Imperfecta includes a group of genetic disorders impacting bone metabolism. Approximately 85% to 90% of OI cases are caused by genetic variants in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. 
  • The collagen mutations in Osteogenesis Imperfecta can result in increased bone brittleness, which contributes to a high rate of fractures. 
  • Patients with Osteogenesis Imperfecta also exhibit inadequate production of new bone and excess bone resorption, resulting in decreased bone mineral density, bone fragility and weakness. 
  • Osteogenesis Imperfectacan also lead to bone deformities, abnormal spine curvature, pain, decreased mobility, and short stature.
  • No treatments are globally approved for Osteogenesis Imperfecta, which affects approximately 60,000 people in commercially accessible geographies.

The human monoclonal antibody: Setrusumab

  • Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, a negative regulator of bone formation. 
  • Blocking sclerostin is expected to increase new bone formation, bone mineral density and bone strength in Osteogenesis Imperfecta. 
  • In mouse models of OI, the use of anti-sclerostin antibodies was shown to increase bone formation, improve bone mass to normal levels, and increase bone strength against fracture force testing to normal levels.

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