Ultragenyx and Mereo said setrusumab failed to meet primary endpoints in two late‑phase trials for brittle bone disease (osteogenesis imperfecta), missing statistically significant reductions in annualized fracture rate despite gains in bone mineral density (BMD). The companies reported Phase III failures in the Orbit and Cosmic trials and flagged differing baseline fracture rates across studies. Ultragenyx noted the BMD improvements replicated earlier Phase II signals but did not translate into the expected fracture reductions, partly due to a low placebo fracture rate in Orbit and non‑significant AFR reductions versus bisphosphonates in Cosmic. The companies announced plans to reassess operations and implement “significant expense reductions.” The outcome will affect pipeline prioritization, investor valuations, and timelines for alternative OI approaches such as gene or anabolic therapies.