1. Both Phase 3 studies for setrusumab missed primary fracture rate endpoints. 2. Significant improvements in bone mineral density were achieved in both studies. 3. Ultragenyx plans significant expense reductions following disappointing results. 4. CEO emphasizes commitment to commercial revenue and future gene therapy launches. 5. No approved treatments exist for Osteogenesis Imperfecta; market remains unmet.
FAQ
Why Bearish?
Missing primary endpoints in clinical trials negatively impacts investor sentiment and stock valuation. Previous similar incidents in biotech have led to drastic stock price declines.
How important is it?
The company's failure to meet primary endpoints directly affects RARE's future prospects, altering investment desirability. Stakeholders may reassess their positions based on these findings, impacting the stock price.
Why Short Term?
Initial market reactions to trial results usually manifest quickly within days or weeks. Similar past events saw immediate sell-offs in biotech companies post-announcement.
Ultragenyx Announces Phase 3 Orbit and Cosmic Results for Setrusumab (UX143) in Osteogenesis Imperfecta
NOVATO, Calif., Dec. 29, 2025 (GLOBE NEWSWIRE) — Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) has revealed the results from its Phase 3 Orbit and Cosmic studies for setrusumab (UX143) targeting Osteogenesis Imperfecta (OI). Unfortunately, neither study achieved its primary endpoint of reducing the annualized clinical fracture rate when compared to placebo in the Orbit study, or against bisphosphonates in the Cosmic study. However, both studies did achieve significant improvements in bone mineral density (BMD), underscoring the drug's potential efficacy in this area.
Study Results Analysis
Despite the disappointment regarding the primary endpoints, the studies demonstrated notable improvements in BMD.
- The **Orbit study** evidenced substantial and statistically significant enhancements in BMD compared to placebo.
- The **Cosmic study** showed meaningful BMD improvements in a younger patient demographic, but without statistically significant reductions in fracture rates compared to bisphosphonates.
Emil Kakkis, M.D., Ph.D., CEO and President of Ultragenyx, expressed his concern, stating, “We are surprised and disappointed by these results given the promising data from our Phase 2 study and the lack of approved treatment options available to patients with OI who live with significant pain, disability, and disease burden.” He affirmed that the company will delve into further analyses to better understand the outcomes.
Operational Changes and Future Directions
In light of these results, Ultragenyx is set to implement considerable expense reductions. Dr. Kakkis noted, “While we are disappointed by these results, we continue to build our commercial revenue from four approved products and prepare for a transformational year ahead with potentially two near-term gene therapy launches and a pivotal Phase 3 readout in Angelman syndrome.”
About the Setrusumab Phase 3 Program
The development of setrusumab (UX143) includes two late-stage studies focusing on pediatric and young adult patients across OI sub-types I, III, and IV.
- The **Orbit study**, a global, seamless Phase 2/3 trial, involved **159 patients** aged **5 to 25 years**, randomized **2:1** to receive either setrusumab or placebo.
- The **Cosmic study** involved **69 patients** aged **2 to <7 years**, randomized **1:1** to receive setrusumab or intravenous bisphosphonates (IV-BP).
Understanding Osteogenesis Imperfecta (OI)
OI is a group of genetic disorders that significantly impact bone metabolism. Around **85% to 90%** of cases are attributed to genetic variants in the COL1A1 or COL1A2 genes. This results in fragile bones due to abnormal collagen production, leading to a high fragility fracture rate. Currently, no treatments are approved worldwide for OI, which affects approximately **60,000** individuals in commercially accessible regions.
About Ultragenyx
Ultragenyx is a biopharmaceutical company committed to developing innovative treatments for serious rare and ultra-rare genetic diseases. Its portfolio includes several approved therapies aiming at unmet medical needs. The company is led by an experienced management team focused on efficient drug development to deliver effective therapies to patients swiftly.
Forward-Looking Statements
The information presented here contains forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. These statements involve substantial risks and uncertainties that may affect the company's clinical development, future results, and operational objectives, including its plans concerning UX143.