Ultragenyx Pharmaceutical has reported that its Phase 3 Orbit and Cosmic studies of setrusumab (UX143) in patients with osteogenesis imperfecta (OI) failed to meet their primary endpoints.
The trials did not show a statistically significant reduction in annualized clinical fracture rates compared to placebo or bisphosphonates, the pharma company has said.
However, both studies did demonstrate improvements in bone mineral density (BMD) against comparators, and no new safety concerns emerged.
“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,” said Emil Kakkis, chief executive officer and president of Ultragenyx.
"We continue to explore the data to gain deeper understanding of the findings.”
In the Orbit study, participants experienced statistically significant improvements in BMD compared to placebo, consistent with Phase 2 results. But these gains did not translate into lower fracture rates, partly due to a low fracture incidence in the placebo group.
The Cosmic study, conducted in younger patients with higher baseline fracture rates, showed meaningful BMD improvements and a trend toward reduced fractures in setrusumab-treated patients compared to those on bisphosphonates—but the reduction fell short of statistical significance.
Ultragenyx plans additional analyses across both studies, including evaluation of other bone health and clinical endpoints beyond fractures, to determine next steps.
In response to the trial outcomes, Ultragenyx said it will implement significant expense reductions while continuing to expand commercial revenue from its four approved products.
“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,” Dr Kakkis said.
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