London & Novato, Calif. — December 2025
Mereo BioPharma Group plc (NASDAQ: MREO) and Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced topline results from their pivotal Phase 3 clinical trials of setrusumab (UX143)—an investigational therapy for Osteogenesis Imperfecta (OI), a rare genetic disorder characterized by brittle bones and recurrent fractures.
The ORBIT and COSMIC studies did not achieve their primary endpoints of statistically significant reduction in annualized clinical fracture rates in patients treated with setrusumab compared to control groups. The ORBIT study enrolled adolescents and young adults, while the COSMIC study enrolled pediatric patients aged 2 to <7.
Despite these outcomes:
- Both trials met key secondary endpoints, showing statistically significant improvements in bone mineral density (BMD) among treated patients.
- No new safety issues were identified across either study.
Executive Comments
Dr. Denise Scots-Knight, CEO of Mereo BioPharma, said:
“While reaching the primary fracture endpoint remains our goal, the improvements in bone mineral density are encouraging and support further analysis, particularly in younger patients. We remain committed to generating deeper insights from this data to inform the path forward for patients living with OI.”
Emil D. Kakkis, M.D., Ph.D., CEO and President of Ultragenyx, added:
“The primary endpoint results are disappointing, especially given the significant unmet need in Osteogenesis Imperfecta. However, the treatment’s consistent safety profile and positive secondary outcomes highlight important biological activity that merits thoughtful evaluation as we consider next steps.”
Context and Next Steps
Osteogenesis Imperfecta affects tens of thousands of individuals worldwide and currently has no globally approved targeted therapies. The companies will undertake additional analyses, including subgroup evaluations and deeper exploration of fracture trends, to better understand the drivers of the results and to guide potential future development strategies.
Both organizations reaffirm their commitment to supporting the OI community, including sharing detailed clinical trial data with regulatory authorities, investigators, patients, and caregivers.
About Setrusumab (UX143)
Setrusumab is a fully human monoclonal antibody designed to inhibit sclerostin—a regulator of bone metabolism—intended to increase new bone formation and strength. It has been studied in multiple international clinical sites across pediatric and young adult patients with OI.
About Mereo BioPharma Group plc
Mereo BioPharma is a clinical-stage biopharmaceutical company focused on developing transformative therapies for rare diseases and oncology. The company is headquartered in London and listed on NASDAQ (MREO).
About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company dedicated to developing novel treatments for rare and ultra-rare diseases, leveraging scientific innovation to address high-unmet medical needs. The company is headquartered in Novato, California, and listed on NASDAQ (RARE).
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