Ultragenyx and Mereo reported that setrusumab, an anti‑sclerostin antibody for osteogenesis imperfecta, missed primary fracture‑rate endpoints in the Phase III portions of the Orbit and Cosmic trials. While both trials saw statistically significant gains in bone mineral density, those improvements did not translate into statistically significant reductions in annualized clinical fracture rates across primary comparisons. Ultragenyx said it will “promptly define and implement significant expense reductions” following the readouts. The negative top‑line results highlight the divergence that can occur between surrogate endpoints (BMD) and clinical outcomes (fracture rate) and will trigger portfolio and cost reassessments at both companies.