Ultragenyx Bone Drug Stumbles In Phase 3, But Key Catalysts Remain

Core Viewpoint - Ultragenyx Pharmaceutical Inc. shares fell 42% following disappointing late-stage data for their rare bone disease program in collaboration with Mereo BioPharma Group plc [1] Group 1: Study Results - The Phase 3 Orbit and Cosmic studies for setrusumab (UX143) in Osteogenesis Imperfecta (OI) did not achieve statistical significance for the primary endpoints of reducing annualized clinical fracture rate compared to placebo or bisphosphonates [2] - Both studies met secondary endpoints, showing improvements in bone mineral density (BMD) against comparators, with no changes in the safety profile observed [2] Group 2: Analyst Reactions - Analysts from William Blair expressed disappointment and surprise at the results, especially given setrusumab's efficacy in the Phase 2 portion of the Orbit study and the increased enrollment of patients with severe disease subtypes in the Phase 3 study [3] - Analyst Sami Corwin is cautious about the future of setrusumab, noting several unknowns regarding the data, including potential effects in pediatric patients and the unexpectedly low annualized fracture rate in the placebo arm [4] Group 3: Market Impact and Future Outlook - Following the news, Ultragenyx is trading at a value reflective of its approved products, with William Blair maintaining an Outperform rating for the stock [4] - There is potential for upside in the next 12 months, particularly with the pivotal Angelman syndrome readout expected in Q3 2026 and the potential approval of two gene therapies eligible for priority review vouchers [5]